Prognostic markers in chronic lymphocytic leukemia: A comprehensive review

Blood Reviews

Volumn 23, Issue 1, 2009, Pages 25-47

  Van Bockstaele, Femke ^a   Verhasselt, Bruno ^a   Philippé, Jan ^a  

^a GHENT UNIVERSITY   (Belgium)

Author keywords

CD38; Chronic lymphocytic leukemia (CLL); Cytogenetic markers; Mutation status; Prognostic factors; ZAP70

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; BETA 2 MICROGLOBULIN; CD20 ANTIBODY; CD23 ANTIGEN; CD27 ANTIGEN; CD38 ANTIGEN; CYTOKINE; HERMES ANTIGEN; LACTATE DEHYDROGENASE; LIPOPROTEIN LIPASE; MICRORNA; PROTEIN KINASE ZAP 70; THROMBOPOIETIN; THYMIDINE KINASE;

ANGIOGENESIS; ARTICLE; CANCER DIAGNOSIS; CANCER GRADING; CANCER GROWTH; CANCER PATIENT; CANCER RISK; CANCER STAGING; CANCER SURVIVAL; CELL PROLIFERATION; CHROMOSOME ABERRATION; CHROMOSOME DELETION; CHRONIC LYMPHATIC LEUKEMIA; CLL UPREGULATED GENE 1; DISEASE MARKER; GENE; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION;

ANTIGENS, CD38; CYTOGENETIC ANALYSIS; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MEMBRANE GLYCOPROTEINS; MUTATION; TUMOR MARKERS, BIOLOGICAL; ZAP-70 PROTEIN-TYROSINE KINASE;

EID: 58349119794     PISSN: 0268960X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.blre.2008.05.003     Document Type: Article

References (281)

1. Rai K.R., Sawitsky A., Cronkite E.P., et al. Clinical staging of chronic lymphocytic leukemia. Blood 46 (1975) 219-234
2. Rai K.R. A critical analysis of staging in CLL. In: Gale R.P., and Rai K.R. (Eds). Chronic lymphocytic leukemia: recent progress and future directions vol. 59 (1987), Alan R Liss, New York 253-264
3. Binet J.L., Lepoprier M., Dighiero G., et al. A clinical staging system for chronic lymphocytic leukemia: prognostic significance. Cancer 40 (1977) 855-864
4. Binet J.L., Auquier A., Dighiero G., et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48 (1981) 198-206
5. Lee J.S., Dixon D.O., Kantarjian H.M., et al. Prognosis of chronic lymphocytic leukemia: a multivariate regression analysis of 325 untreated patients. Blood 69 (1987) 929-936
6. Catovsky D., Fooks J., and Richards S. Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults. Br J Haematol 72 (1989) 141-149
7. Montserrat E., Gomis F., Vallespi T., et al. Presenting features and prognosis of chronic lymphocytic leukemia in younger adults. Blood 78 (1991) 1545-1551
8. Molica S. Sex differences in incidence and outcome of chronic lymphocytic leukemia patients. Leuk Lymphoma 47 (2006) 1477-1480
9. Jaksic B., Vitale B., Hauptmann E., et al. The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases. Br J Cancer 64 (1991) 345-348
10. Mauro F.R., Foa R., Giannarelli D., et al. Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood 94 (1999) 448-454
11. Molica S., Brugiatelli M., Callea V., et al. Comparison of younger versus older B-cell chronic lymphocytic leukemia patients for clinical presentation and prognosis. A retrospective study of 53 cases. Eur J Haematol 52 (1994) 216-221
12. Dominis M., and Jaksic B. Clinical relevance of peripheral blood lymphocyte morphology and lymph node histology in chronic lymphocytic leukemia. Blood Cells 12 (1987) 297-313
13. Schwarz J., Mikulenkova D., Cermakova M., et al. Prognostic relevance of the FAB morphological criteria in chronic lymphocytic leukemia: correlations with IgVH gene mutational status and other prognostic markers. Neoplasma 53 (2006) 219-225
14. Vallespi T., Montserrat E., and Sanz M.A. Chronic lymphocytic leukaemia: prognostic value of lymphocyte morphological subtypes. A multivariate survival analysis in 146 patients. Br J Haematol 77 (1991) 478-485
15. Han T., Barcos M., Emrich L., et al. Bone marrow infiltration patterns and their prognostic significance in chronic lymphocytic leukemia: correlations with clinical, immunologic, phenotypic, and cytogenetic data. J Clin Oncol 2 (1984) 562-570
16. Rozman C., Hernandez-Nieto L., Montserrat E., et al. Prognostic significance of bone-marrow patterns in chronic lymphocytic leukaemia. Br J Haematol 47 (1981) 529-537
17. Rozman C., Montserrat E., Rodriguez-Fernandez J.M., et al. Bone marrow histologic pattern-the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases. Blood 64 (1984) 642-648
18. Dohner H., Stilgenbauer S., Benner A., et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343 (2000) 1910-1916
19. Durig J., Naschar M., Schmucker U., et al. CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia 16 (2002) 30-35
20. Schroers R., Griesinger F., Trumper L., et al. Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia. Leukemia 19 (2005) 750-758
21. Di Giovanni S., Valentini G., Carducci P., et al. Beta-2-microglobulin is a reliable tumor marker in chronic lymphocytic leukemia. Acta Haematol 81 (1989) 181-185
22. Hallek M., Wanders L., Ostwald M., et al. Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leuk Lymphoma 22 (1996) 439-447
23. Molica S., Levato D., Cascavilla N., et al. Clinico-prognostic implications of simultaneous increased serum levels of soluble CD23 and beta2-microglobulin in B-cell chronic lymphocytic leukemia. Eur J Haematol 62 (1999) 117-122
24. Del Poeta G., Maurillo L., Venditti A., et al. Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 98 (2001) 2633-2639
25. Heintel D., Schwarzinger I., Chizzali-Bonfadin C., et al. Association of CD38 antigen expression with other prognostic parameters in early stages of chronic lymphocytic leukemia. Leuk Lymphoma 42 (2001) 1315-1321
26. Del Principe M.I., Del Poeta G., Buccisano F., et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood 108 (2006) 853-861
27. Durig J., Nuckel H., Cremer M., et al. ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia. Leukemia 17 (2003) 2426-2434
28. Sarfati M., Chevret S., Chastang C., et al. Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia. Blood 88 (1996) 4259-4264
29. Knauf W.U., Langenmayer I., Ehlers B., et al. Serum levels of soluble CD23, but not soluble CD25, predict disease progression in early stage B-cell chronic lymphocytic leukemia. Leuk Lymphoma 27 (1997) 523-532
30. Molica S., Levato D., Dell'Olio M., et al. Cellular expression and serum circulating levels of CD23 in B-cell chronic lymphocytic leukemia. Implications for prognosis. Haematologica 81 (1996) 428-433
31. Saka B., Aktan M., Sami U., et al. Prognostic importance of soluble CD23 in B-cell chronic lymphocytic leukemia. Clin Lab Haematol 28 (2006) 30-35
32. van Oers M.H., Pals S.T., Evers L.M., et al. Expression and release of CD27 in human B-cell malignancies. Blood 82 (1993) 3430-3436
33. Molica S., Vitelli G., Levato D., et al. CD27 in B-cell chronic lymphocytic leukemia. Cellular expression, serum release and correlation with other soluble molecules belonging to nerve growth factor receptors (NGFr) superfamily. Haematologica 83 (1998) 398-402
34. Manshouri T., Do K.A., Wang X., et al. Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood 101 (2003) 2507-2513
35. De Rossi G., Marroni P., Paganuzzi M., et al. Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia. Leukemia 11 (1997) 134-141
36. Eisterer W., Bechter O., Soderberg O., et al. Elevated levels of soluble CD44 are associated with advanced disease and in vitro proliferation of neoplastic lymphocytes in B-cell chronic lymphocytic leukaemia. Leuk Res 28 (2004) 1043-1051
37. Molica S., Vitelli G., Levato D., et al. Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression. Cancer 92 (2001) 713-719
38. Fayad L., Keating M.J., Reuben J.M., et al. Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood 97 (2001) 256-263
39. Kara I.O., Sahin B., and Gunesacar R. Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic lymphocytic leukemia: correlation with disease stage and prognosis. Adv Ther 24 (2007) 29-40
40. Lai R., O'Brien S., Maushouri T., et al. Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer 95 (2002) 1071-1075
41. Molica S., Vitelli G., Levato D., et al. Clinico-biological implications of increased serum levels of interleukin-8 in B-cell chronic lymphocytic leukemia. Haematologica 84 (1999) 208-211
42. Wierda W.G., Johnson M.M., Do K.A., et al. Plasma interleukin 8 level predicts for survival in chronic lymphocytic leukaemia. Br J Haematol 120 (2003) 452-456
43. Koller C., Bekele B.N., Zhou X., et al. Plasma thrombopoietin compared with immunoglobulin heavy-chain mutation status as a predictor of survival in chronic lymphocytic leukemia. Blood 108 (2006) 1001-1006
44. Molica S., Vitelli G., Cutrona G., et al. Serum thrombopoietin compared with ZAP-70 and immunoglobulin heavy-chain gene mutation status as a predictor of time to first treatment in early chronic lymphocytic leukemia. Leuk Lymphoma 49 (2008) 62-67
45. Messmer B.T., Messmer D., Allen S.L., et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest 115 (2005) 755-764
46. Montserrat E., Sanchez-Bisono J., Vinolas N., et al. Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. Br J Haematol 62 (1986) 567-575
47. Molica S., and Alberti A. Prognostic value of the lymphocyte doubling time in chronic lymphocytic leukemia. Cancer 60 (1987) 2712-2716
48. Kallander C.F., Simonsson B., Hagberg H., et al. Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia. Cancer 54 (1984) 2450-2455
49. Hallek M., Langenmayer I., Nerl C., et al. Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood 93 (1999) 1732-1737
50. Magnac C., Porcher R., Davi F., et al. Predictive value of serum thymidine kinase level for Ig-V mutational status in B-CLL. Leukemia 17 (2003) 133-137
51. Bechter O.E., Eisterer W., Pall G., et al. Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Res 58 (1998) 4918-4922
52. Damle R.N., Batliwalla F.M., Ghiotto F., et al. Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood 103 (2004) 375-382
53. Ishibe N., Prieto D., Hosack D.A., et al. Telomere length and heavy-chain mutation status in familial chronic lymphocytic leukemia. Leuk Res 26 (2002) 791-794
54. Verstovsek S., Giles F.J., O'Brien S., et al. Telomerase activity is not a prognostic factor in chronic lymphocytic leukemia. Leuk Res 28 (2004) 707-711
55. Tchirkov A., Chaleteix C., Magnac C., et al. hTERT expression and prognosis in B-chronic lymphocytic leukemia. Ann Oncol 15 (2004) 1476-1480
56. Terrin L., Trentin L., Degan M., et al. Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. Leukemia 21 (2007) 965-972
57. Roos G., Krober A., Grabowski P., et al. Short telomeres are associated with genetic complexity, high risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood 111 (2008) 2246-2252
58. Ricca I., Rocci A., Drandi D., et al. Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients. Leukemia 21 (2007) 697-705
59. Grabowski P., Hultdin M., Karlsson K., et al. Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood 105 (2005) 4807-4812
60. Hultdin M., Rosenquist R., Thunberg U., et al. Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications. Br J Cancer 88 (2003) 593-598
61. Chen H., Treweeke A.T., West D.C., et al. In vitro and in vivo production of vascular endothelial growth factor by chronic lymphocytic leukemia cells. Blood 96 (2000) 3181-3187
62. Kini A.R., Kay N.E., and Peterson L.C. Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia. Leukemia 14 (2000) 1414-1418
63. Molica S., Vacca A., Ribatti D., et al. Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia. Blood 100 (2002) 3344-3351
64. Aguayo A., O'Brien S., Keating M., et al. Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia. Blood 96 (2000) 768-770
65. Duensing S., and Atzpodien J. Increased intracellular and plasma levels of basic fibroblast growth factor in B-cell chronic lymphocytic leukemia. Blood 85 (1995) 1978-1980
66. Gora-Tybor J., Blonski J.Z., and Robak T. Circulating proangiogenic cytokines and angiogenesis inhibitor endostatin in untreated patients with chronic lymphocytic leukemia. Mediators Inflamm 12 (2003) 167-171
67. Kay N.E., Bone N.D., Tschumper R.C., et al. B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules. Leukemia 16 (2002) 911-919
68. Menzel T., Rahman Z., Calleja E., et al. Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood 87 (1996) 1056-1063
69. Molica S., Vitelli G., Levato D., et al. Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia. Br J Haematol 107 (1999) 605-610
70. Molica S., Vitelli G., Levato D., et al. Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblastic growth factor in early B-cell chronic lymphocytic leukaemia. Br J Cancer 86 (2002) 31-35
71. Molica S., Cutrona G., Vitelli G., et al. Markers of increased angiogenesis and their correlation with biological parameters identifying high-risk patients in early B-cell chronic lymphocytic leukemia. Leuk Res 31 (2007) 1575-1578
72. Huttmann A., Klein-Hitpass L., Thomale J., et al. Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression status. Leukemia 20 (2006) 1774-1782
73. McCabe D., Bacon L., O'Regan K., et al. CD38 expression on B-cell chronic lymphocytic leukemic cells is strongly correlated with vascular endothelial growth factor expression. Leukemia 18 (2004) 649-650
74. Smolej L., Andrys C., Pekova S., et al. Plasma levels of basic fibroblast growth factor and vascular endothelial growth factor and their association with IgVH mutation status in patients with B-cell chronic lymphocytic leukemia. Haematologica 91 (2006) 1432-1433
75. Smolej L., Andrys C., and Vroblova V. Modern prognostic factors and angiogenesis in chronic lymphocytic leukemia: More data needed. Leuk Res 31 (2007) 1763-1764
76. Maffei R., Marasca R., Martinelli S., et al. Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status. Leukemia 21 (2007) 1312-1315
77. Martinelli S., Maffei R., Castelli I., et al. Increased expression of angiopoietin-2 characterizes early B-cell chronic lymphocytic leukemia with poor prognosis. Leuk Res 32 (2008) 593-597
78. Molica S., Vitelli G., Levato D., et al. Serum angiogenin is not elevated in patients with early B-cell chronic lymphocytic leukemia but is prognostic factor for disease progression. Eur J Haematol 73 (2004) 36-42
79. Ferrajoli A., Manshouri T., Estrov Z., et al. High levels of vascular endothelial growth factor receptor-2 correlate with shortened survival in chronic lymphocytic leukemia. Clin Cancer Res 7 (2001) 795-799
80. Molica S., Vitelli G., Levato D., et al. Increased serum levels of matrix metalloproteinase-9 predict clinical outcome of patients with early B-cell chronic lymphocytic leukaemia. Eur J Haematol 70 (2003) 373-378
81. Kamiguti A.S., Lee E.S., Till K.J., et al. The role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia. Br J Haematol 125 (2004) 128-140
82. Molica S., Vitelli G., Mirabelli R., et al. Serum levels of syndecan-1 in B-cell chronic lymphocytic leukemia: correlation with the extent of angiogenesis and disease-progression risk in early disease. Leuk Lymphoma 47 (2006) 1034-1040
83. Jilani I., Wei C., Bekele B.N., et al. Soluble syndecan-1 (sCD138) as a prognostic factor independent of mutation status in patients with chronic lymphocytic leukemia. Int J Lab Hematol (2008)
84. Autio K., Turunen O., Pentillä O., et al. Human chronic lymphocytic leukemia: karyotypes in different lymphocyte populations. Cancer Genet Cytogenet 1 (1979) 147-155
85. Robert K.H., Moller E., Gahrton G., et al. B-cell activation of peripheral blood lymphocytes from patients with chronic lymphatic leukaemia. Clin Exp Immunol 33 (1978) 302-308
86. Hurley J.N., Fu S.M., Kunkel H.G., et al. Chromosome abnormalities of leukaemic B lymphocytes in chronic lymphocytic leukaemia. Nature 283 (1980) 76-78
87. Gahrton G., Robert K.H., Friberg K., et al. Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation. Blood 56 (1980) 640-647
88. Gahrton G., Robert K.H., Friberg K., et al. Extra chromosome 12 in chronic lymphocytic leukaemia. Lancet 1 (1980) 146-147
89. Buhmann R., Kurzeder C., Rehklau J., et al. CD40L stimulation enhances the ability of conventional metaphase cytogenetics to detect chromosome aberrations in B-cell chronic lymphocytic leukaemia cells. Br J Haematol 118 (2002) 968-975
90. Mayr C., Speicher M.R., Kofler D.M., et al. Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia. Blood 107 (2006) 742-751
91. Dicker F., Schnittger S., Haferlach T., et al. Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood 108 (2006) 3152-3160
92. Haferlach C., Dicker F., Schnittger S., et al. Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia 21 (2007) 2442-24451
93. Bentz M., Huck K., du Manoir S., et al. Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses. Blood 85 (1995) 3610-3618
94. Dewald G.W., Brockman S.R., Paternoster S.F., et al. Chromosome anomalies detected by interphase fluorescence in situ hybridization: correlation with significant biological features of B-cell chronic lymphocytic leukaemia. Br J Haematol 121 (2003) 287-295
95. Dohner H., Stilgenbauer S., James M.R., et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood 89 (1997) 2516-2522
96. Glassman A.B., and Hayes K.J. The value of fluorescence in situ hybridization in the diagnosis and prognosis of chronic lymphocytic leukemia. Cancer Genet Cytogenet 158 (2005) 88-91
97. Krober A., Seiler T., Benner A., et al. V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood 100 (2002) 1410-1416
98. Oscier D.G., Gardiner A.C., Mould S.J., et al. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood 100 (2002) 1177-1184
99. Dohner H., Fischer K., Bentz M., et al. p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood 85 (1995) 1580-1589
100. Neilson J.R., Auer R., White D., et al. Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival. Leukemia 11 (1997) 1929-1932
101. Robert K.H., Gahrton G., Friberg K., et al. Extra chromosome 12 and prognosis in chronic lymphocytic leukaemia. Scand J Haematol 28 (1982) 163-168
102. Juliusson G., Oscier D.G., Fitchett M., et al. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. N Engl J Med 323 (1990) 720-724
103. Gaidano G., Newcomb E.W., Gong J.Z., et al. Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia. Am J Pathol 144 (1994) 1312-1319
104. Wattel E., Preudhomme C., Hecquet B., et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 84 (1994) 3148-3157
105. Cano I., Martinez J., Quevedo E., et al. Trisomy 12 and p53 deletion in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: association with morphology and resistance to conventional chemotherapy. Cancer Genet Cytogenet 90 (1996) 118-124
106. el Rouby S., Thomas A., Costin D., et al. p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression. Blood 82 (1993) 3452-3459
107. Sturm I., Bosanquet A.G., Hermann S., et al. Mutation of p53 and consecutive selective drug resistance in B-CLL occurs as a consequence of prior DNA-damaging chemotherapy. Cell Death Differ 10 (2003) 477-484
108. Byrd J.C., Gribben J.G., Peterson B.L., et al. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol 24 (2006) 437-443
109. Austen B., Powell J.E., Alvi A., et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood 106 (2005) 3175-3182
110. Bullrich F., Rasio D., Kitada S., et al. ATM mutations in B-cell chronic lymphocytic leukemia. Cancer Res 59 (1999) 24-27
111. Stankovic T., Weber P., Stewart G., et al. Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia. Lancet 353 (1999) 26-29
112. Schaffner C., Stilgenbauer S., Rappold G.A., et al. Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 94 (1999) 748-753
113. Delmer A., Ajchenbaum-Cymbalista F., Tang R., et al. Overexpression of cyclin D2 in chronic B-cell malignancies. Blood 85 (1995) 2870-2876
114. Haidar M.A., El-Hajj H., Bueso-Ramos C.E., et al. Expression profile of MDM-2 proteins in chronic lymphocytic leukemia and their clinical relevance. Am J Hematol 54 (1997) 189-195
115. Watanabe T., Hotta T., Ichikawa A., et al. The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. Blood 84 (1994) 3158-3165
116. Calin G.A., Dumitru C.D., Shimizu M., et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99 (2002) 15524-15529
117. Cimmino A., Calin G.A., Fabbri M., et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102 (2005) 13944-13949
118. Cuneo A., Rigolin G.M., Bigoni R., et al. Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis. Leukemia 18 (2004) 476-483
119. Oscier D.G., Stevens J., Hamblin T.J., et al. Correlation of chromosome abnormalities with laboratory features and clinical course in B-cell chronic lymphocytic leukaemia. Br J Haematol 76 (1990) 352-358
120. Stilgenbauer S., Bullinger L., Benner A., et al. Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia. Leukemia 13 (1999) 1331-1334
121. Pittman S., and Catovsky D. Prognostic significance of chromosome abnormalities in chronic lymphocytic leukaemia. Br J Haematol 58 (1984) 649-660
122. Ross F.M., and Stockdill G. Clonal chromosome abnormalities in chronic lymphocytic leukemia patients revealed by TPA stimulation of whole blood cultures. Cancer Genet Cytogenet 25 (1987) 109-121
123. Dickinson J.D., Joshi A., Iqbal J., et al. Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a gene dosage effect. Int J Mol Med 17 (2006) 769-778
124. Dyer M.J., and Oscier D.G. The configuration of the immunoglobulin genes in B cell chronic lymphocytic leukemia. Leukemia 16 (2002) 973-984
125. Callet-Bauchu E., Salles G., Gazzo S., et al. Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome. Leukemia 13 (1999) 460-468
126. Cavazzini F., Cuneo A., de Angeli C., et al. Abnormalities of chromosomes 1p34-36, 4p16, 4q35, 9q11-32 and +7 represent novel recurrent cytogenetic rearrangements in chronic lymphocytic leukemia. Leuk Lymphoma 45 (2004) 1197-1203
127. Michaux L, Wlodarska I, Rack K et al. Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in "unmutated" B-CLL. Leukemia 2005;19:77-82.
128. Ripolles L., Ortega M., Ortuno F., et al. Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia. Cancer Genet Cytogenet 171 (2006) 57-64
129. Van Den Neste E., Robin V., Francart J., et al. Chromosomal translocations independently predict treatment failure, treatment-free survival and overall survival in B-cell chronic lymphocytic leukemia patients treated with cladribine. Leukemia 21 (2007) 1715-1722
130. Stilgenbauer S., Bullinger L., Lichter P., et al. Genetics of chronic lymphocytic leukemia: genomic aberrations and V(H) gene mutation status in pathogenesis and clinical course. Leukemia 16 (2002) 993-1007
131. Chevallier P., Penther D., Avet-Loiseau H., et al. CD38 expression and secondary 17p deletion are important prognostic factors in chronic lymphocytic leukaemia. Br J Haematol 116 (2002) 142-150
132. Fegan C., Robinson H., Thompson P., et al. Karyotypic evolution in CLL: identification of a new sub-group of patients with deletions of 11q and advanced or progressive disease. Leukemia 9 (1995) 2003-2008
133. Finn W.G., Kay N.E., Kroft S.H., et al. Secondary abnormalities of chromosome 6q in B-cell chronic lymphocytic leukemia: a sequential study of karyotypic instability in 51 patients. Am J Hematol 59 (1998) 223-229
134. Oscier D., Fitchett M., Herbert T., et al. Karyotypic evolution in B-cell chronic lymphocytic leukaemia. Genes Chromosomes Cancer 3 (1991) 16-20
135. Shanafelt T.D., Witzig T.E., Fink S.R., et al. Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. J Clin Oncol 24 (2006) 4634-4641
136. Stilgenbauer S., Sander S., Bullinger L., et al. Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica 92 (2007) 1242-1245
137. MacLennan I.C. Germinal centers. Annu Rev Immunol 12 (1994) 117-139
138. MacLennan I.C. Somatic mutation. From the dark zone to the light. Curr Biol 4 (1994) 70-72
139. Shaffer A.L., Rosenwald A., and Staudt L.M. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2 (2002) 920-932
140. Caligaris-Cappio F. B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. Blood 87 (1996) 2615-2620
141. Kipps T.J., Tomhave E., Pratt L.F., et al. Developmentally restricted immunoglobulin heavy chain variable region gene expressed at high frequency in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 86 (1989) 5913-5917
142. Meeker T.C., Grimaldi J.C., O'Rourke R., et al. Lack of detectable somatic hypermutation in the V region of the Ig H chain gene of a human chronic B lymphocytic leukemia. J Immunol 141 (1988) 3994-3998
143. Kuppers R., Gause A., and Rajewsky K. B cells of chronic lymphatic leukemia express V genes in unmutated form. Leuk Res 15 (1991) 487-496
144. Schroeder Jr. H.W., and Dighiero G. The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunol Today 15 (1994) 288-294
145. Fais F., Ghiotto F., Hashimoto S., et al. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 102 (1998) 1515-1525
146. Oscier D.G., Thompsett A., Zhu D., et al. Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. Blood 89 (1997) 4153-4160
147. Hamblin T.J., Davis Z., Gardiner A., et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94 (1999) 1848-1854
148. Damle R.N., Wasil T., Fais F., et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94 (1999) 1840-1847
149. Jelinek D.F., Tschumper R.C., Geyer S.M., et al. Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia. Br J Haematol 115 (2001) 854-861
150. Matrai Z., Lin K., Dennis M., et al. CD38 expression and Ig VH gene mutation in B-cell chronic lymphocytic leukemia. Blood 97 (2001) 1902-1903
151. Hamblin T.J., Orchard J.A., Ibbotson R.E., et al. CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood 99 (2002) 1023-1029
152. Lin K., Sherrington P.D., Dennis M., et al. Relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation in chronic lymphocytic leukemia. Blood 100 (2002) 1404-1409
153. Tobin G., Thunberg U., Johnson A., et al. Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia. Blood 99 (2002) 2262-2264
154. Ghia P., Guida G., Stella S., et al. The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood 101 (2003) 1262-1269
155. Tobin G., Thunberg U., Johnson A., et al. Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vlambda2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope. Blood 101 (2003) 4952-4957
156. Vasconcelos Y., Davi F., Levy V., et al. Binet's staging system and VH genes are independent but complementary prognostic indicators in chronic lymphocytic leukemia. J Clin Oncol 21 (2003) 3928-3932
157. Aleskog A., Tobin G., Laurell A., et al. VH gene mutation status and cellular drug resistance in chronic lymphocytic leukaemia. Eur J Haematol 73 (2004) 407-411
158. Marasca R., Maffei R., Morselli M., et al. Immunoglobulin mutational status detected through single-round amplification of partial V(H) region represents a good prognostic marker for clinical outcome in chronic lymphocytic leukemia. J Mol Diagn 7 (2005) 566-574
159. Tobin G., Thunberg U., Laurell A., et al. Patients with chronic lymphocytic leukemia with mutated VH genes presenting with Binet stage B or C form a subgroup with a poor outcome. Haematologica 90 (2005) 465-469
160. Thorselius M., Krober A., Murray F., et al. Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood 107 (2006) 2889-2894
161. Lin K., Manocha S., Harris R.J., et al. High frequency of p53 dysfunction and low level of VH mutation in chronic lymphocytic leukemia patients using the VH3-21 gene segment. Blood 102 (2003) 1145-1146
162. Ghia P., Stamatopoulos K., Belessi C., et al. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia 21 (2007) 1-3
163. Lefranc MP. IMGT databases, web resources and tools for immunoglobulin and T cell receptor sequence analysis, http://imgt.cines.fr. Leukemia 2003; 17: 260-6.
164. Davi F., Rosenquist R., Ghia P., et al. Determination of IGHV gene mutational status in chronic lymphocytic leukemia: bioinformatics advances meet clinical needs. Leukemia 22 (2008) 212-214
165. Lane B.S., Mensah A.A., Lin K., et al. Analysis of VH gene sequences using two web-based immunogenetics resources gives different results, but the affinity maturation status of chronic lymphocytic leukaemia clones as assessed from either of the resulting data sets has no prognostic significance. Leukemia 19 (2005) 741-749
166. Pekova S., Baran-Marszak F., Schwarz J., et al. Mutated or non-mutated? Which database to choose when determining the IgVH hypermutation status in chronic lymphocytic leukemia?. Haematologica 91 (2006) ELT01
167. Rassenti L.Z., and Kipps T.J. Lack of allelic exclusion in B cell chronic lymphocytic leukemia. J Exp Med 185 (1997) 1435-1445
168. Rassenti L.Z., and Kipps T.J. Expression of Ig-beta (CD79b) by chronic lymphocytic leukemia B cells that lack immunoglobulin heavy-chain allelic exclusion. Blood 95 (2000) 2725-2727
169. Thunberg U., Johnson A., Roos G., et al. CD38 expression is a poor predictor for VH gene mutational status and prognosis in chronic lymphocytic leukemia. Blood 97 (2001) 1892-1894
170. Bilban M., Heintel D., Scharl T., et al. Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression. Leukemia 20 (2006) 1080-1088
171. Haslinger C., Schweifer N., Stilgenbauer S., et al. Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status. J Clin Oncol 22 (2004) 3937-3949
172. Jelinek D.F., Tschumper R.C., Stolovitzky G.A., et al. Identification of a global gene expression signature of B-chronic lymphocytic leukemia. Mol Cancer Res 1 (2003) 346-361
173. Klein U., Tu Y., Stolovitzky G.A., et al. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med 194 (2001) 1625-1638
174. Rosenwald A., Alizadeh A.A., Widhopf G., et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 194 (2001) 1639-1647
175. Vasconcelos Y., De Vos J., Vallat L., et al. Gene expression profiling of chronic lymphocytic leukemia can discriminate cases with stable disease and mutated Ig genes from those with progressive disease and unmutated Ig genes. Leukemia 19 (2005) 2002-2005
176. Deaglio S., Vaisitti T., Aydin S., et al. In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia. Blood 108 (2006) 1135-1144
177. Wiestner A., Rosenwald A., Barry T.S., et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood 101 (2003) 4944-4951
178. Hayat A., O'Brien D., O'Rourke P., et al. CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia. Leuk Lymphoma 47 (2006) 2371-2379
179. Hamblin T.J., Orchard J.A., Gardiner A., et al. Immunoglobulin V genes and CD38 expression in CLL. Blood 95 (2000) 2455-2457
180. Domingo-Domenech E., Domingo-Claros A., Gonzalez-Barca E., et al. CD38 expression in B-chronic lymphocytic leukemia: association with clinical presentation and outcome in 155 patients. Haematologica 87 (2002) 1021-1027
181. D'Arena G., Musto P., Cascavilla N., et al. CD38 expression correlates with adverse biological features and predicts poor clinical outcome in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 42 (2001) 109-114
182. Thornton P.D., Fernandez C., Giustolisi G.M., et al. CD38 expression as a prognostic indicator in chronic lymphocytic leukaemia. Hematol J 5 (2004) 145-151
183. Ibrahim S., Keating M., Do K.A., et al. CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood 98 (2001) 181-186
184. Gentile M., Mauro F.R., Calabrese E., et al. The prognostic value of CD38 expression in chronic lymphocytic leukaemia patients studied prospectively at diagnosis: a single institute experience. Br J Haematol 130 (2005) 549-557
185. Chang C.C., and Cleveland R.P. Conversion of CD38 and/or myeloid-associated marker expression status during the course of B-CLL: association with a change to an aggressive clinical course. Blood 100 (2002) 1106
186. Matrai Z. CD38 as a prognostic marker in CLL. Hematology 10 (2005) 39-46
187. Ghia P., Guida G., Scielzo C., et al. CD38 modifications in chronic lymphocytic leukemia: are they relevant?. Leukemia 18 (2004) 1733-1735
188. Dignum H.M., Summerfield G.P., Proctor S.J., et al. Quantification of CD38 expression in B-cell chronic lymphocytic leukemia (B-CLL): a comparison between antibody binding capacity (ABC) and relative median fluorescence (RMF). Leuk Lymphoma 45 (2004) 1167-1173
189. Hsi E.D., Kopecky K.J., Appelbaum F.R., et al. Prognostic significance of CD38 and CD20 expression as assessed by quantitative flow cytometry in chronic lymphocytic leukaemia. Br J Haematol 120 (2003) 1017-1025
190. Mainou-Fowler T., Dignum H., Taylor P.R., et al. Quantification improves the prognostic value of CD38 expression in B-cell chronic lymphocytic leukaemia. Br J Haematol 118 (2002) 755-761
191. Morabito F., Mangiola M., Oliva B., et al. Peripheral blood CD38 expression predicts survival in B-cell chronic lymphocytic leukemia. Leuk Res 25 (2001) 927-932
192. Cutrona G., Colombo M., Matis S., et al. B lymphocytes in humans express ZAP-70 when activated in vivo. Eur J Immunol 36 (2006) 558-569
193. Nolz J.C., Tschumper R.C., Pittner B.T., et al. ZAP-70 is expressed by a subset of normal human B-lymphocytes displaying an activated phenotype. Leukemia 19 (2005) 1018-1024
194. Crespo M., Villamor N., Gine E., et al. ZAP-70 expression in normal pro/pre B cells, mature B cells, and in B-cell acute lymphoblastic leukemia. Clin Cancer Res 12 (2006) 726-734
195. Guillaume N., Alleaume C., Munfus D., et al. ZAP-70 tyrosine kinase is constitutively expressed and phosphorylated in B-lineage acute lymphoblastic leukemia cells. Haematologica 90 (2005) 899-905
196. Admirand J.H., Rassidakis G.Z., Abruzzo L.V., et al. Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma. Mod Pathol 17 (2004) 954-961
197. Chiaretti S., Guarini A., De Propris M.S., et al. ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications. Blood 107 (2006) 197-204
198. Scielzo C., Camporeale A., Geuna M., et al. ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage. Leukemia 20 (2006) 689-695
199. Sup S.J., Domiati-Saad R., Kelley T.W., et al. ZAP-70 expression in B-cell hematologic malignancy is not limited to CLL/SLL. Am J Clin Pathol 122 (2004) 582-587
200. Crespo M., Bosch F., Villamor N., et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 348 (2003) 1764-1775
201. Kim S.Z., Chow K.U., Kukoc-Zivojnov N., et al. Expression of ZAP-70 protein correlates with disease stage in chronic lymphocytic leukemia and is associated with, but not generally restricted to, non-mutated Ig VH status. Leuk Lymphoma 45 (2004) 2037-2045
202. Orchard J.A., Ibbotson R.E., Davis Z., et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363 (2004) 105-111
203. Rassenti L.Z., Huynh L., Toy T.L., et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351 (2004) 893-901
204. Carreras J., Villamor N., Colomo L., et al. Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid neoplasms. J Pathol 205 (2005) 507-513
205. Del Giudice I., Morilla A., Osuji N., et al. Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia. Cancer 104 (2005) 2124-2132
206. Laurenti L., Petlickovski A., Rumi C., et al. Comparison of ZAP-70/Syk mRNA levels with immunoglobulin heavy-chain gene mutation status and disease progression in chronic lymphocytic leukemia. Haematologica 90 (2005) 1533-1540
207. Hus I., Podhorecka M., Bojarska-Junak A., et al. The clinical significance of ZAP-70 and CD38 expression in B-cell chronic lymphocytic leukaemia. Ann Oncol 17 (2006) 683-690
208. Krober A., Bloehdorn J., Hafner S., et al. Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 24 (2006) 969-975
209. Vener C., Gianelli U., Cortelezzi A., et al. ZAP-70 immunoreactivity is a prognostic marker of disease progression in chronic lymphocytic leukemia. Leuk Lymphoma 47 (2006) 245-251
210. D'Arena G., Tarnani M., Rumi C., et al. Prognostic significance of combined analysis of ZAP-70 and CD38 in chronic lymphocytic leukemia. Am J Hematol 82 (2007) 787-791
211. Stamatopoulos B., Meuleman N., Haibe-Kains B., et al. Quantification of ZAP70 mRNA in B cells by real-time PCR is a powerful prognostic factor in chronic lymphocytic leukemia. Clin Chem 53 (2007) 1757-1766
212. Zanotti R., Ambrosetti A., Lestani M., et al. ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase CLL patients, is a strong adverse prognostic factor. Leukemia 21 (2007) 102-109
213. Catherwood M.A., Matthews C., Niblock R., et al. ZAP-70 mRNA quantification in B-cell chronic lymphocytic leukaemia. Eur J Haematol 76 (2006) 294-298
214. Van Bockstaele F., Janssens A., Piette A., et al. Kolmogorov-Smirnov statistical test for analysis of ZAP-70 expression in B-CLL, compared with quantitative PCR and IgV(H) mutation status. Cytometry B Clin Cytom 70 (2006) 302-308
215. Munoz L., Lasa A., Carricondo M.T., et al. Comparative analysis of ZAP-70 expression and Ig VH mutational status in B-cell chronic lymphocytic leukemia. Cytometry B Clin Cytom 72 (2007) 96-102
216. Gibbs G., Bromidge T., Howe D., et al. Comparison of flow cytometric methods for the measurement of ZAP-70 expression in a routine diagnostic laboratory. Clin Lab Haematol 27 (2005) 258-266
217. Poulain S., Benard C., Daudignon A., et al. Is ZAP-70 expression stable over time in B chronic lymphocytic leukaemia?. Leuk Lymphoma 48 (2007) 1219-1221
218. Chen Z., Aston E., and Yu M.K. Loss of Zap-70 and low molecular weight phosphotyrosine phosphatase occurs after therapy in a patient with B-chronic lymphocytic leukemia. Leukemia 19 (2005) 1503-1505
219. Chaar B.T., Grosso L., and Petruska P.J. Variability of ZAP 70 expression in a patient with CLL. Am J Hematol 81 (2006) 645
220. Bakke A.C., Purtzer Z., Leis J., et al. A robust ratio metric method for analysis of Zap-70 expression in chronic lymphocytic leukemia (CLL). Cytometry B Clin Cytom 70 (2006) 227-234
221. Best O.G., Ibbotson R.E., Parker A.E., et al. ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants, and methods of analysis. Cytometry B Clin Cytom 70 (2006) 235-241
222. Chen Y.H., Peterson L.C., Dittmann D., et al. Comparative analysis of flow cytometric techniques in assessment of ZAP-70 expression in relation to IgVH mutational status in chronic lymphocytic leukemia. Am J Clin Pathol 127 (2007) 182-191
223. Kay S., Herishanu Y., Pick M., et al. Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia using molecules of equivalent soluble fluorochrome. Cytometry B Clin Cytom 70 (2006) 218-226
224. Letestu R., Rawstron A., Ghia P., et al. Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process. Cytometry B Clin Cytom 70 (2006) 309-314
225. Passam F., Tachynopoulou V., Skoumi D., et al. Feasibility of an easily applicable method of ZAP-70 measurement in chronic lymphocytic leukemia in the routine flow cytometry setting: A methodological approach. Ann Hematol 85 (2006) 795-805
226. Shankey T.V., Forman M., Scibelli P., et al. An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemia. Cytometry B Clin Cytom 70 (2006) 259-269
227. Ferrer A., Ollila J., Tobin G., et al. Different gene expression in immunoglobulin-mutated and immunoglobulin-unmutated forms of chronic lymphocytic leukemia. Cancer Genet Cytogenet 153 (2004) 69-72
228. Oppezzo P., Vasconcelos Y., Settegrana C., et al. The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia. Blood 106 (2005) 650-657
229. Heintel D., Kienle D., Shehata M., et al. High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia. Leukemia 19 (2005) 1216-1223
230. Nuckel H., Huttmann A., Klein-Hitpass L., et al. Lipoprotein lipase expression is a novel prognostic factor in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 47 (2006) 1053-1061
231. van't Veer M.B., Brooijmans A.M., Langerak A.W., et al. The predictive value of lipoprotein lipase for survival in chronic lymphocytic leukemia. Haematologica 91 (2006) 56-63
232. Nikitin E.A., Malakho S.G., Biderman B.V., et al. Expression level of lipoprotein lipase and dystrophin genes predict survival in B-cell chronic lymphocytic leukemia. Leuk Lymphoma 48 (2007) 912-922
233. Van Bockstaele F., Pede V., Janssens A., et al. Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia. Clin Chem 53 (2007) 204-212
234. Pallasch C.P., Schwamb J., Konigs S., et al. Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells. Leukemia 22 (2008) 585-592
235. Li F.J., Ding S., Pan J., et al. FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia. Blood (2008)
236. Benedetti D., Bomben R., Dal-Bo M., et al. Are surrogates of IGHV gene mutational status useful in B-cell chronic lymphocytic leukemia? The example of Septin-10. Leukemia 22 (2008) 224-226
237. Kainz B., Shehata M., Bilban M., et al. Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia. Int J Cancer 121 (2007) 1984-1993
238. Albesiano E., Messmer B.T., Damle R.N., et al. Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone. Blood 102 (2003) 3333-3339
239. Heintel D., Kroemer E., Kienle D., et al. High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia. Leukemia 18 (2004) 756-762
240. McCarthy H., Wierda W.G., Barron L.L., et al. High expression of activation-induced cytidine deaminase (AID) and splice variants is a distinctive feature of poor-prognosis chronic lymphocytic leukemia. Blood 101 (2003) 4903-4908
241. Oppezzo P., Vuillier F., Vasconcelos Y., et al. Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation. Blood 101 (2003) 4029-4032
242. Buhl A.M., Jurlander J., Jorgensen F.S., et al. Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. Blood 107 (2006) 2904-2911
243. Buhl A.M., Jurlander J., Pedersen L.B., et al. A novel and disease specific gene in chronic lymphocytic leukemia. Blood 104 (2004) 770 [ASH annual meeting abstracts]
244. Buhl A.M., Jurlander J., Geisler C.H., et al. CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia. Eur J Haematol 76 (2006) 455-464
245. Chen L., Li J., Zheng W., et al. The prognostic evaluation of CLLU1 expression levels in 50 Chinese patients with chronic lymphocytic leukemia. Leuk Lymphoma 48 (2007) 1785-1792
246. Josefsson P., Geisler C.H., Leffers H., et al. CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood 109 (2007) 4973-4979
247. Bechter O.E., Eisterer W., Dlaska M., et al. CpG island methylation of the hTERT promoter is associated with lower telomerase activity in B-cell lymphocytic leukemia. Exp Hematol 30 (2002) 26-33
248. Raval A., Lucas D.M., Matkovic J.J., et al. TWIST2 demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia. J Clin Oncol 23 (2005) 3877-3885
249. Corcoran M., Parker A., Orchard J., et al. ZAP-70 methylation status is associated with ZAP-70 expression status in chronic lymphocytic leukemia. Haematologica 90 (2005) 1078-1088
250. Calin G.A., Liu C.G., Sevignani C., et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101 (2004) 11755-11760
251. Calin G.A., Ferracin M., Cimmino A., et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353 (2005) 1793-1801
252. Fulci V., Chiaretti S., Goldoni M., et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood 109 (2007) 4944-4951
253. Marton S., Garcia M.R., Robello C., et al. Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia 22 (2008) 330-338
254. Pekarsky Y., Santanam U., Cimmino A., et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 66 (2006) 11590-11593
255. Eksioglu-Demiralp E., Alpdogan O., Aktan M., et al. Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages. Leukemia 10 (1996) 1331-1339
256. Zucchetto A., Sonego P., Degan M., et al. Surface-antigen expression profiling (SEP) in B-cell chronic lymphocytic leukemia (B-CLL): identification of markers with prognostic relevance. J Immunol Methods 305 (2005) 20-32
257. Gattei V., Bulian P., Del Principe M.I., et al. Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood 111 (2008) 865-873
258. Pittner B.T., Shanafelt T.D., Kay N.E., et al. CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation. Leukemia 19 (2005) 2264-2272
259. Shanafelt T.D., Geyer S.M., Bone N.D., et al. CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol 140 (2008) 537-546
260. Zucchetto A., Bomben R., Dal Bo M., et al. CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and prognostic relevance. Leukemia 20 (2006) 523-525 author reply 8-9
261. Herishanu Y., Kay S., Rogowski O., et al. T-cell ZAP-70 overexpression in chronic lymphocytic leukemia (CLL) correlates with CLL cell ZAP-70 levels, clinical stage and disease progression. Leukemia 19 (2005) 1289-1291
262. Tinhofer I., Rubenzer G., Holler C., et al. Expression levels of CD38 in T cells predict course of disease in male patients with B-chronic lymphocytic leukemia. Blood 108 (2006) 2950-2956
263. Scielzo C., Ghia P., Conti A., et al. HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J Clin Invest 115 (2005) 1644-1650
264. Matthews C., Catherwood M.A., Larkin A.M., et al. MDR-1, but not MDR-3 gene expression, is associated with unmutated IgVH genes and poor prognosis chromosomal aberrations in chronic lymphocytic leukemia. Leuk Lymphoma 47 (2006) 2308-2313
265. Ocana E., Delgado-Perez L., Campos-Caro A., et al. The prognostic role of CXCR3 expression by chronic lymphocytic leukemia B cells. Haematologica 92 (2007) 349-356
266. Nuckel H., Rebmann V., Durig J., et al. HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia. Blood 105 (2005) 1694-1698
267. Rebmann V., Nuckel H., Duhrsen U., et al. HLA-G in B-chronic lymphocytic leukaemia: clinical relevance and functional implications. Semin Cancer Biol 17 (2007) 430-435
268. Perez-Chacon G., Rosado S., Rebolleda N., et al. Prognostic irrelevance of HLA-G in B-cell chronic lymphocytic leukemia. Int J Lab Hematol (2008)
269. Esteve J., Villamor N., Colomer D., et al. Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia 15 (2001) 445-451
270. Moreno C., Villamor N., Colomer D., et al. Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood 107 (2006) 4563-4569
271. Moreton P., Kennedy B., Lucas G., et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 23 (2005) 2971-2979
272. Provan D., Bartlett-Pandite L., Zwicky C., et al. Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 88 (1996) 2228-2235
273. Rawstron A.C., Kennedy B., Evans P.A., et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 98 (2001) 29-35
274. Wendtner C.M., Ritgen M., Schweighofer C.D., et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission-experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia 18 (2004) 1093-1101
275. Bottcher S., Ritgen M., Pott C., et al. Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation. Leukemia 18 (2004) 1637-1645
276. Bosch F., Ferrer A., Lopez-Guillermo A., et al. Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. Br J Haematol 119 (2002) 976-984
277. Rawstron A.C., Villamor N., Ritgen M., et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 21 (2007) 956-964
278. Sayala H.A., Rawstron A.C., and Hillmen P. Minimal residual disease assessment in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 20 (2007) 499-512
279. Montillo M., Schinkoethe T., and Elter T. Eradication of minimal residual disease with alemtuzumab in B-cell chronic lymphocytic leukemia (B-CLL) patients: the need for a standard method of detection and the potential impact of bone marrow clearance on disease outcome. Cancer Invest 23 (2005) 488-496
280. Cheson B.D., Bennett J.M., Grever M., et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87 (1996) 4990-4997
281. Hallek M, Cheson BD, Catovsky D et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) updating the National Cancer Institute-Working Group (NCI-WG) 1996 guidelines. Blood 2008;111:5446-56.