The cytogenetics and molecular biology of the myelodysplastic syndromes

Myelodysplastic Syndromes: Pathobiology and Clinical Management, Second Edition

Volumn , Issue , 2008, Pages 49-86

  Olney, Harold J ^a   Le Beau, Michelle M ^b  

^a NOTRE DAME HOSPITAL   (Canada)

^b UNIVERSITY OF CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0141499687     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (146)

1. Vardiman JW. The new World Health Organization classification of myeloid neoplasms: Q&Awith JamesW.Vardiman, MD.Clin Adv Hematol Oncol 2003; 1:18,21.
2. Cazzola M, Malcovati L. Myelodysplastic syndromes-Coping with ineffective hematopoiesis. N Engl J Med 2005; 352:536-538.
3. Bowen D, Culligan D, Jowitt S, et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 2003; 120:187-200.
4. Jaffe ES HN, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001.
5. Vallespi T, Imbert M, Mecucci C, et al. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica 1998; 83:258-275.
6. Spitzer G, Verma DS, Dicke KA, et al. Subgroups of oligoleukemia as identified by in vitro agar culture. Leuk Res 1979; 3:29-39.
7. Wells DA, Benesch M, Loken MR, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood 2003; 102:394-403.
8. van de Loosdrecht AA, Westers TM, Westra AH, et al. Identification of distinct prognostic subgroups in low and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood 2008; 111:1067-1077.
9. Kussick SJ, Fromm JR, Rossini A, et al. Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia. Am J Clin Pathol 2005; 124:170-181.
10. Walker J, Flower D, Rigley K. Microarrays in hematology. Curr Opin Hematol 2002; 9:23-29.
11. Gondek LP, Tiu R, O’Keefe CL, et al. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood 2008; 111:1534-1542.
12. Van den Berghe H, Michaux L. 5q-, twenty-five years later: A synopsis. Cancer Genet Cytogenet 1997; 94:1-7.
13. Jary L, Mossafa H, Fourcade C, et al. The 17p-syndrome: A distinct myelodysplastic syndrome entity? Leuk Lymphoma 1997; 25:163-168.
14. Dewald GW, Pierre RV, Phyliky RL. Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia. Blood 1982; 59:100-105.
15. Rowley JD. The role of chromosome translocations in leukemogenesis. Semin Hematol 1999; 36:59-72.
16. Gozzetti A, Le Beau MM. Fluorescence in situ hybridization: Uses and limitations. Semin Hematol 2000; 37:320-333.
17. Kearney L. The impact of the new fish technologies on the cytogenetics of haematological malignancies. Br J Haematol 1999; 104:648-658.
18. Jotterand M, Parlier V. Diagnostic and prognostic significance of cytogenetics in adult primary myelodysplastic syndromes. Leuk Lymphoma 1996; 23:253-266.
19. Morel P, Hebbar M, Lai JL, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: A report on 408 cases. Leukemia 1993; 7:1315-1323.
20. Sole F, Luno E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica 2005; 90:1168-1178.
21. Toyama K, Ohyashiki K, Yoshida Y, et al. Clinical and cytogenetic findings of myelodysplastic syndromes showing hypocellular bone marrow or minimal dysplasia, in comparison with typical myelodysplastic syndromes. Int J Hematol 1993; 58:53-61.
22. Haase D, Germing U, Schanz J, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007; 110:4385-4395.
23. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89:2079-2088.
24. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007; 25:3503-3510.
25. Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 2008; 22:538-543.
26. Apperley JF, Gardembas M, Melo JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002; 347:481-487.
27. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006; 355:1456-1465.
28. Hamblin TJ, Oscier DG. The myelodysplastic syndrome-A practical guide. Hematol Oncol 1987; 5:19-34.
29. de Souza Fernandez T, Ornellas MH, Otero de Carvalho L, et al. Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia. Leuk Res 2000; 24:839-848.
30. Geddes AA, Bowen DT, Jacobs A. Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome. Br J Haematol 1990; 76:194-202.
31. Horiike S, Taniwaki M, Misawa S, et al. Chromosome abnormalities and karyotypic evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis. Cancer 1988; 62:1129-1138.
32. Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom Cancer Cytogenetics Group (UKCCG). Genes Chromosomes Cancer 1992; 5:83-88.
33. Wiktor A, Rybicki BA, Piao ZS, et al. Clinical significance of Y chromosome loss in hematologic disease. Genes Chromosomes Cancer 2000; 27:11-16.
34. Wattel E, Lai JL, Hebbar M, et al. De novo myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 20: A subtype of MDS with distinct hematological and prognostic features? Leuk Res 1993; 17:921-926.
35. Kurtin PJ, Dewald GW, Shields DJ, et al. Hematologic disorders associated with deletions of chromosome 20q: A clinicopathologic study of 107 patients. Am J Clin Pathol 1996; 106:680-688.
36. Godley LA, Larson RA. The syndrome of therapy-related myelodysplasia and myeloid leukemia. In: Bennett JM, ed. The Myelodysplastic Syndromes: Pathobiology and Clinical Management. New York: Marcel Dekker Inc., 2002:136-176.
37. West RR, Stafford DA, White AD, et al. Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure. Blood 2000; 95:2093-2097.
38. AulC, BowenDT, YoshidaY. Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica 1998; 83:71-86.
39. Larson RA, LeBeau MM, Vardiman JW, et al. Myeloid leukemia after hematotoxins. Environ Health Perspect 1996; 104(Suppl. 6):1303-1307.
40. McCarthy CJ, Sheldon S, Ross CW, et al. Cytogenetic abnormalities and therapyrelated myelodysplastic syndromes in rheumatic disease. Arthritis Rheum 1998; 41:1493-1496.
41. Pedersen-Bjergaard J, Andersen MK, Christiansen DH. Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood 2000; 95:3273-3279.
42. Hayes RB, Yin SN, Dosemeci M, et al. Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese Academy of Preventive Medicine- National Cancer Institute Benzene Study Group. J Natl Cancer Inst 1997; 89:1065-1071.
43. Fenaux P, Lucidarme D, Lai JL, et al. Favorable cytogenetic abnormalities in secondary leukemia. Cancer 1989; 63:2505-2508.
44. Rowley JD, Olney HJ. International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: Overview report. Genes Chromosomes Cancer 2002; 33:331-345.
45. Boultwood J, Lewis S, Wainscoat JS. The 5q-syndrome. Blood 1994; 84:3253-3260.
46. Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q-syndrome gene by RNA interference screen. Nature 2008; 451:335-339.
47. Paulsson K, Sall T, Fioretos T, et al. The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology.Cancer GenetCytogenet 2001; 130:160-165.
48. Paulsson K, Heidenblad M, Strombeck B, et al. High-resolution genome-wide arraybased comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration. Leukemia 2006; 20:840-846.
49. Sole F, Espinet B, Sanz GF, et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 2000; 108:346-356.
50. Kardos G, Baumann I, Passmore SJ, et al. Refractory anemia in childhood: A retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 2003; 102:1997-2003.
51. Luna-Fineman S, Shannon KM, Lange BJ. Childhood monosomy 7: Epidemiology, biology, and mechanistic implications. Blood 1995; 85:1985-1999.
52. Emanuel PD. Myelodysplasia and myeloproliferative disorders in childhood: An update. Br J Haematol 1999; 105:852-863.
53. Martinez-Climent JA, Garcia-Conde J. Chromosomal rearrangements in childhood acute myeloid leukemia and myelodysplastic syndromes. J Pediatr Hematol Oncol 1999; 21:91-102.
54. Bjork J, Albin M, Mauritzson N, et al. Smoking and myelodysplastic syndromes. Epidemiology 2000; 11:285-291.
55. Johansson B, Mertens F, Mitelman F. Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor loci. Genes Chromosomes Cancer 1993; 8:205-218.
56. Lai JL, Preudhomme C, Zandecki M, et al. Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia 1995; 9:370-381.
57. Wang P, Spielberger RT, Thangavelu M, et al. Dic(5; 17): A recurring abnormality in malignant myeloid disorders associated with mutations of TP53. Genes Chromosomes Cancer 1997; 20:282-291.
58. Merlat A, Lai JL, Sterkers Y, et al. Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion. A report on 25 cases. Leukemia 1999; 13:250-257.
59. Thirman MJ, Larson RA. Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 1996; 10:293-320.
60. Le BeauMM, Albain KS, LarsonRA, et al.Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: Further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol 1986; 4:325-345.
61. ZhangY, Rowley JD. Chromatin structural elements and chromosomal translocations in leukemia. DNA Repair (Amst) 2006; 5:1282-1297.
62. Bain BJ, Moorman AV, Johansson B, et al. Myelodysplastic syndromes associated with 11q23 abnormalities. European 11q23Workshop participants. Leukemia 1998; 12:834-839.
63. Secker-Walker LM. General report on the european union concerted actionworkshop on 11q23, London, U.K.: May 1997. Leukemia 1998; 12:776-778.
64. Bloomfield CD, Archer KJ, Mrozek K, et al. 11q23 balanced chromosome aberrations in treatment-related myelodysplastic syndromes and acute leukemia: Report from an international workshop. Genes Chromosomes Cancer 2002; 33:362-378.
65. Rowley JD, Reshmi S, Sobulo O, et al. All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997; 90:535-541.
66. Golub TR, Barker GF, Lovett M, et al. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994; 77:307-316.
67. Ross TS, Bernard OA, Berger R, et al. Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2). Blood 1998; 91:4419-4426.
68. Magnusson MK, Meade KE, Brown KE, et al. Rabaptin-5 is a novel fusion partner to platelet-derived growth factor beta receptor in chronic myelomonocytic leukemia. Blood 2001; 98:2518-2525.
69. Kulkarni S, Heath C, Parker S, et al. Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21). Cancer Res 2000; 60:3592-3598.
70. Abe A, Emi N, Tanimoto M, et al. Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Blood 1997; 90:4271-4277.
71. Rubin CM, Larson RA, Bitter MA, et al. Association of a chromosomal 3;21 translocation with the blast phase of chronic myelogenous leukemia. Blood 1987; 70:1338-1342.
72. Rubin CM, Larson RA, Anastasi J, et al. t(3;21)(q26;q22): A recurring chromosomal abnormality in therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood 1990; 76:2594-2598.
73. Sood R, Talwar-Trikha A, Chakrabarti SR, et al. MDS1/EVI1 enhances TGFbeta1 signaling and strengthens its growth-inhibitory effect but the leukemiaassociated fusion protein AML1/MDS1/EVI1, product of the t(3;21), abrogates growth-inhibition in response to TGF-beta1. Leukemia 1999; 13:348-357.
74. Martinelli G, Ottaviani E, Buonamici S, et al. Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica 2003; 88:1221-1228.
75. Pekarsky Y, Rynditch A, Wieser R, et al. Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia. Cancer Res 1997; 57:3914-3919.
76. Block AW, Carroll AJ, Hagemeijer A, et al. Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: Report from an international workshop. Genes Chromosomes Cancer 2002; 33:401-412.
77. Knudson AG Jr. Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68:820-823.
78. Venkatachalam S, Shi YP, Jones SN, et al. Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. EMBO J 1998; 17:4657-4667.
79. Rosenbauer F, Wagner K, Kutok JL, et al. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat Genet 2004; 36:624-630.
80. Song WJ, Sullivan MG, Legare RD, et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 1999; 23:166-175.
81. French JE, Lacks GD, Trempus C, et al. Loss of heterozygosity frequency at theTrp53 locus in p53-deficient (+/-) mouse tumors is carcinogen-and tissue-dependent. Carcinogenesis 2001; 22:99-106.
82. Fero ML, Rivkin M, Tasch M, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 1996; 85:733-744.
83. Michaud J, Wu F, Osato M, et al. In vitro analyses of knownand novelRUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: Implications for mechanisms of pathogenesis. Blood 2002; 99:1364-1372.
84. Nakao M, Horiike S, Fukushima-Nakase Y, et al. Novel loss-of-function mutations of the haematopoiesis-related transcription factor, acute myeloid leukaemia 1/runt-related transcription factor 1, detected in acute myeloblastic leukaemia and myelodysplastic syndrome. Br J Haematol 2004; 125:709-719.
85. Lai F, Godley LA, Joslin J, et al. Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q). Genomics 2001; 71:235-245.
86. Fairman J, Chumakov I, Chinault AC, et al. Physical mapping of the minimal region of loss in 5q-chromosome. Proc Natl Acad Sci U S A 1995; 92:7406-7410.
87. Horrigan SK, Arbieva ZH, Xie HY, et al. Delineation of a minimal interval and identification of 9 candidates for a tumor suppressor gene in malignant myeloid disorders on 5q31. Blood 2000; 95:2372-2377.
88. Zhao N, Stoffel A, Wang PW, et al. Molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases to 1-1.5 Mb and preparation of a PAC-based physical map. Proc Natl Acad Sci U S A 1997; 94:6948-6953.
89. Joslin JM, Fernald AA, Tennant TR, et al. Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders. Blood 2007; 110:719-726.
90. Liu TX, Becker MW, Jelinek J, et al. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med 2007; 13:78-83.
91. Boultwood J, Fidler C, Strickson AJ, et al. Narrowing and genomic annotation of the commonly deleted region of the 5q-syndrome. Blood 2002; 99:4638-4641.
92. Le BeauMM, EspinosaR III, Davis EM, et al. Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases. Blood 1996; 88:1930-1935.
93. Fischer K, Frohling S, Scherer SW, et al. Molecular cytogenetic delineation of deletions and translocations involving chromosome band 7q22 in myeloid leukemias. Blood 1997; 89:2036-2041.
94. Tosi S, Scherer SW, Giudici G, et al. Delineation of multiple deleted regions in 7q in myeloid disorders. Genes Chromosomes Cancer 1999; 25:384-392.
95. CurtissNP, Bonifas JM, Lauchle JO, et al. Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22. Genomics 2005; 85:600-607.
96. Döhner K, Habdank M, Rucker FG, et al. Molecular characterization of distinct hot spot regins on chromosome 7q in myeloid leukemias. Blood 2006; 108; Abstract 2349.
97. Bench AJ, Nacheva EP, Hood TL, et al. Chromosome 20 deletions in myeloid malignancies: Reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes. UK Cancer Cytogenetics Group (UKCCG). Oncogene 2000; 19:3902-3913.
98. Wang PW, Eisenbart JD, Espinosa R III, et al. Refinement of the smallest commonly deleted segment of chromosome 20 in malignant myeloid diseases and development of a PAC-based physical and transcription map. Genomics 2000; 67:28-39.
99. MacGrogan D, Kalakonda N, Alvarez S, et al. Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells. Genes Chromosomes Cancer 2004; 41:203-213.
100. Neubauer A, Greenberg P, Negrin R, et al. Mutations in the ras proto-oncogenes in patients with myelodysplastic syndromes. Leukemia 1994; 8:638-641.
101. Beaupre DM, Kurzrock R. RAS and leukemia: From basic mechanisms to genedirected therapy. J Clin Oncol 1999; 17:1071-1079.
102. Padua RA, Guinn BA, Al-Sabah AI, et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: A 10-year follow-up. Leukemia 1998; 12:887-892.
103. de Souza Fernandez T, Menezes de Souza J, Macedo Silva ML, et al. Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myelodysplastic syndrome. Leuk Res 1998; 22:125-134.
104. Tien HF, Wang CH, Chuang SM, et al. Cytogenetic studies, ras mutation, and clinical characteristics in primary myelodysplastic syndrome.Astudy on 68 Chinese patients in Taiwan. Cancer Genet Cytogenet 1994; 74:40-49.
105. Bacher U, Haferlach T, KernW, et al. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007; 92:744-752.
106. Kurzrock R, Kantarjian HM, Cortes JE, et al. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: Clinical and biologic activities in the phase 1 setting. Blood 2003; 102:4527-4534.
107. Chen CY, Lin LI, Tang JL, et al. RUNX1 gene mutation in primary myelodysplastic syndrome-The mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome. Br J Haematol 2007; 139:405-414.
108. Niimi H, Harada H, Harada Y, et al. Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia 2006; 20:635-644.
109. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352:254-266.
110. Pedersen-Bjergaard J, Andersen MT, Andersen MK. Genetic pathways in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2007; 2007:392-397.
111. Shiseki M, Kitagawa Y, Wang YH, et al. Lack of nucleophosmin mutation in patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. Leuk Lymphoma 2007; 48:2141-2144.
112. Leroy H, Roumier C, Huyghe P, et al. CEBPA point mutations in hematological malignancies. Leukemia 2005; 19:329-334.
113. Shih LY, Huang CF, Lin TL, et al. Heterogeneous patterns of CEBPalpha mutation status in the progression of myelodysplastic syndrome and chronic myelomonocytic leukemia to acute myelogenous leukemia. Clin Cancer Res 2005; 11:1821-1826.
114. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001; 19:1405-1413.
115. Kita-Sasai Y, Horiike S, Misawa S, et al. International prognostic scoring system and TP53 mutations are independent prognostic indicators for patients with myelodysplastic syndrome. Br J Haematol 2001; 115:309-312.
116. Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617 F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106:1207-1209.
117. Zipperer E, Wulfert M, Germing U, et al. MPL 515 and JAK2 mutation analysis in MDS presenting with a platelet count of more than 500 × 10(9)/l. Ann Hematol 2008; 87:413-415.
118. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Methylation of p15INK4B is common, is associated with deletion of genes on chromosome arm 7q and predicts a poor prognosis in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2003; 17:1813-1819.
119. Pedersen-Bjergaard J, Andersen MK, Christiansen DH, et al. Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia. Blood 2002; 99:1909-1912.
120. Kelly LM, Gilliland DG. Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 2002; 3:179-198.
121. Loh ML, Vattikuti S, Schubbert S, et al. Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis. Blood 2004; 103:2325-2331.
122. Side LE, Curtiss NP, Teel K, et al. RAS, FLT3, and TP53 mutations in therapyrelated myeloid malignancies with abnormalities of chromosomes 5 and 7. Genes Chromosomes Cancer 2004; 39:217-223.
123. Qian Z, Fernald AA, Godley LA, et al. Expression profiling of CD34+ hematopoietic stem/progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia. Proc Natl Acad Sci U S A 2002; 99:14925-14930.
124. Pellagatti A, Cazzola M, Giagounidis AA, et al. Gene expression profiles of CD34+ cells in myelodysplastic syndromes: Involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype. Blood 2006; 108:337-345.
125. Hofmann WK, de Vos S, Komor M, et al. Characterization of gene expression of CD34+ cells from normal and myelodysplastic bone marrow. Blood 2002; 100:3553-3560.
126. Boultwood J, Pellagatti A, Cattan H, et al. Gene expression profiling of CD34+ cells in patients with the 5q-syndrome. Br J Haematol 2007; 139:578-589.
127. Nilsson L, Eden P, Olsson E, et al. The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes. Blood 2007; 110:3005-3014.
128. Parker JE, Mufti GJ, Rasool F, et al. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood 2000; 96:3932-3938.
129. Lepelley P, Soenen V, Preudhomme C, et al. Bcl-2 expression in myelodysplastic syndromes and its correlation with hematological features, p53 mutations and prognosis. Leukemia 1995; 9:726-730.
130. Ridge SA, Worwood M, Oscier D, et al. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA 1990; 87:1377-1380.
131. Kiyoi H, Towatari M, Yokota S, et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia 1998; 12:1333-1337.
132. Horiike S, Yokota S, Nakao M, et al. Tandem duplications of the FLT3 receptor gene are associated with leukemic transformation of myelodysplasia. Leukemia 1997; 11:1442-1446.
133. Tidow N, Kasper B, Welte K. Clinical implications of G-CSF receptor mutations. Crit Rev Oncol Hematol 1998; 28:1-6.
134. Arland M, FiedlerW, Samalecos A, et al. Absence of point mutations in a functionally important part of the extracellular domain of the c-kit proto-oncogene in a series of patients with acute myeloid leukemia (AML). Leukemia 1994; 8:498-501.
135. Siitonen T, Savolainen ER, Koistinen P. Expression of the c-kit proto-oncogene in myeloproliferative disorders and myelodysplastic syndromes. Leukemia 1994; 8:631-637.
136. Zochbauer S, Gsur A, Gotzl M, et al. MDR1 gene expression in myelodysplastic syndrome and in acute myeloid leukemia evolving from myelodysplastic syndrome. Anticancer Res 1994; 14:1293-1295.
137. Faderl S, Kantarjian HM, Estey E, et al. The prognostic significance of p16(INK4 a)/p14(ARF) locus deletion and MDM-2 protein expression in adult acute myelogenous leukemia. Cancer 2000; 89:1976-1982.
138. Bueso-Ramos CE, Manshouri T, Haidar MA, et al. Multiple patterns of MDM-2 deregulation in human leukemias: Implications in leukemogenesis and prognosis. Leuk Lymphoma 1995; 17:13-18.
139. Ogata K, Tamura H. Thrombopoietin and myelodysplastic syndromes. Int J Hematol 2000; 72:173-177.
140. Bouscary D, Preudhomme C, Ribrag V, et al. Prognostic value of c-mpl expression in myelodysplastic syndromes. Leukemia 1995; 9:783-788.
141. Shannon KM, O’Connell P, Martin GA, et al. Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N Engl J Med 1994; 330:597-601.
142. Gallagher A, Darley RL, Padua R. The molecular basis of myelodysplastic syndromes. Haematologica 1997; 82:191-204.
143. Xu D, Gruber A, Peterson C, et al. Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia. Br J Haematol 1998; 102:1367-1375.
144. Li B, Yang J, Andrews C, et al. Telomerase activity in preleukemia and acute myelogenous leukemia. Leuk Lymphoma 2000; 36:579-587.
145. Misawa S, Horiike S. TP53 mutations in myelodysplastic syndrome. Leuk Lymphoma 1996; 23:417-422.
146. Cilloni D, Saglio G.WT1as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Haematol 2004; 112:79-84.