Acute promyelocytic leukemia: A model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia

Leukemia

Volumn 16, Issue 10, 2002, Pages 1959-1973

  Grimwade, D ^a   Lo Coco, F ^b  

^a UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Acute promyelocytic leukemia (APL); Minimal residual disease (MRD); Real time quantitative RT PCR (RQ PCR); RT PCR

Indexed keywords

ANTHRACYCLINE; ARSENIC TRIOXIDE; GEMTUZUMAB OZOGAMICIN; HISTONE DEACETYLASE INHIBITOR; IODINE 131; MONOCLONAL ANTIBODY; NUCLEAR PROTEIN; NUCLEOPHOSMIN; RETINOIC ACID; RETINOIC ACID RECEPTOR ALPHA; RETINOID; SODIUM PHENYLBUTYRATE; STAT5B PROTEIN; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; BLOOD CLOTTING DISORDER; CHROMOSOME TRANSLOCATION 15; CHROMOSOME TRANSLOCATION 17; CONTROLLED STUDY; CYTOGENETICS; DIAGNOSTIC ACCURACY; DRUG FORMULATION; DRUG RESPONSE; DRUG SENSITIVITY; GENE INSERTION; GENE REARRANGEMENT; HUMAN; KARYOTYPING; MEDICAL DOCUMENTATION; MINIMAL RESIDUAL DISEASE; MOLECULAR DYNAMICS; MOLECULAR GENETICS; PATHOGENESIS; PATIENT MONITORING; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROMYELOCYTIC LEUKEMIA; QUANTITATIVE ANALYSIS; RELIABILITY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; STANDARDIZATION;

EID: 0036798706     PISSN: 08876924     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.leu.2402721     Document Type: Review

References (146)

1. Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F. AIDA (All trans retinoic acid + Idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood 1996; 88: 1390-1398.
2. Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood 1999; 93: 4131-4143.
3. Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayón C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all trans retinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. Blood 1999; 94: 1192-1200.
4. Sanz MA, Martín G, Rayón C, Esteve J, González M, Díaz-Mediavilla J, Bolufer P, Barragán E, Terol MJ, González JD, Colomer D, Chillón C, Rivas C, Gómez T, Ribera JM, Bornstein R, Román J, Calasanz MJ, Arias J, Álvarez C, Ramos F, Debén G. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARα-positive acute promyelocytic leukemia. Blood 1999; 94: 3015-3021.
5. Fenaux P, Chomienne C, Degos L. Treatment of acute promyelocytic leukemia. Baillière's Best Pract Res Clin Haematol 2001; 14: 153-174.
6. Kanamaru A, Takemoto Y, Tanimoto M, Murakami H, Asou N, Kobayashi T, Kuriyama K, Ohmoto E, Sakamaki H, Tsubaki K, Hiraoka A, Yamada O, Oh H, Saito K, Matsuda S, Minato K, Ueda T, Ohno R. All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Blood 1995; 85: 1202-1206.
7. Fenaux P, Chomienne C, Degos, L. Acute promyelocytic leukemia: biology and treatment. Semin Oncol 1997; 24: 92-102.
8. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337: 1021-1028.
9. Head D, Kopecky KJ, Weick J, Files J, Ryan D, Foucar K, Montiel M, Bickers J, Fishleder A, Miller M, Spier C, Hanson C, Bitter M, Braziel R, Mills G, Welborn J, Williams W, Hewlett J, Willman C, Appelbaum F. Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia. Blood 1995; 86: 1717-1728.
10. Paietta E, Andersen J, Racevskis J, Gallagher R, Bennett J, Yunis J, Cassileth P, Wiernik PH. Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses. Leukemia 1994; 8: 968-973.
11. Drach D, Zhao S, Drach J, Andreeff M. Low incidence of MDR1 expression in acute promyelocytic leukaemia. Br J Haematol 1995; 90: 369-374.
12. Estey E, Thall PF, Pierce S, Kantarjian H, Keating M. Treatment of newly diagnosed acute promyelocytic leukemia without cytarabine. J Clin Oncol 1997; 15: 483-490.
13. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A, on behalf of the Medical Research Council Adult and Children's Leukaemia Working Parties. The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1612 patients entered into the MRC AML 10 trial. Blood 1998; 92: 2322-2333.
14. Burnett AK, Goldstone AH, Stevens RF, Hann IM, Rees JKH, Gray RG, Wheatley K. Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission: results of MRC AML 10 trial. Lancet 1998; 351: 700-708.
15. Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JKH, Harrison G. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002; 118: 385-400.
16. 3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997; 89: 3354-3360.
17. Soignet SL, Maslak P, Wang Z-G, Jhanwar S, Calleja E, Dardashti LJ, Corso D, deBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. New Engl J Med 1998; 339: 1341-1348.
18. Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, Stone RM, Kalaycio M, Scheinberg DA, Steinherz P, Sievers EL, Coutre S, Dahlberg S, Ellison R, Warrell RP. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol 2001; 19: 3852-3860.
19. Estey EH, Giles FJ, Beran M, O'Brien S, Pierce SA, Faderl SH, Cortes JE, Kantarjian HM. Experience with gemtuzumab ozogamycin ('mylotarg') + all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood 2002; 99: 4222-4224.
20. Rowley JD, Golomb HM, Dougherty C. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1977; 1: 549-550.
21. Larson RA, Kondo K, Vardiman JW, Butler AE, Golomb HM, Rowley JD. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med 1984; 76: 827-841.
22. Borrow J, Goddard AD, Sheer D, Solomon E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science 1990; 249: 1577-1580.
23. de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature 1990; 347: 558-561.
24. de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A. The PML-RARα fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 1991; 66: 675-684.
25. Alcalay M, Zangrilli D, Pandolfi PP, Longo L, Mencarelli A, Giacomucci A, Rocchi M, Biondi A, Rambaldi A, Lo Coco F, Diverio D, Donti E, Grignani F, Pelicci PG. Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor α locus. Proc Natl Acad Sci USA 1991; 88: 1977-1981.
26. Goddard AD, Borrow J, Freemont PS, Solomon E. Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science 1991; 254: 1371-1374.
27. Kakizuka A, Miller WH, Umesono K, Warrell RP, Frankel SR, Murty VVVS, Dmitrovsky E, Evans RM. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML. Cell 1991; 66: 663-674.
28. Piazza F, Gurrieri C, Pandolfi PP. The theory of APL. Oncogene 2001; 20: 7216-7222.
29. Zelent A, Guidez F, Melnick A, Waxman S, Licht JD. Translocations of the RARα gene in acute promyelocytic leukemia. Oncogene 2001; 20: 7186-7203.
30. Kastner P, Chan S. Function of RARα during the maturation of neutrophils. Oncogene 2001; 20: 7178-7185.
31. Lo Coco F, Diverio D, D'Adamo F, Avvisati G, Alimena G, Nanni M, Alcalay M, Pandolfi PP, Pelicci PG. PML/RARα rearrangement in acute promyelocytic leukaemias apparently lacking the t(15;17) translocation. Eur J Haematol 1992; 48: 173-176.
32. Grimwade D, Howe K, Langabeer S, Davies L, Oliver F, Walker H, Swirsky D, Wheatley K, Goldstone A, Burnett A, Solomon E. Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia (APL): cytogenetic, molecular and PML-immunofluorescence assessment of patients entered into the MRC ATRA trial. Br J Haematol 1996; 94: 557-573.
33. Grimwade D, Biondi A, Mozziconacci M-J, Hagemeijer A, Berger R, Neat M, Howe K, Dastugue N, Jansen J, Radford-Weiss I, Lo Coco F, Lessard M, Hernandez J-M, Delabesse E, Head D, Liso V, Sainty D, Flandrin G, Solomon E, Birg F, Lafage-Pochitaloff M. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Blood 2000; 96: 1297-1308.
34. Borrow J, Shipley J, Howe K, Kiely F, Goddard A, Sheer D, Srivastava A, Antony AC, Fioretos T, Mitelman F, Solomon E. Molecular analysis of simple variant translocations in acute promyelocytic leukaemia. Genes Chromosomes Cancer 1994; 9: 234-243.
35. Hiorns LR, Min T, Swansbury GJ, Zelent A, Dyer MJS, Catovsky D. Interstitial insertion of retinoic acid receptor-α gene in acute promyelocytic leukemia with normal chromosomes 15 and 17. Blood 1994; 83: 2946-2951.
36. Lafage-Pochitaloff M, Alcalay M, Brunel V, Longo L, Sainty D, Simonetti J, Birg F, Pelicci PG. Acute promyelocytic leukemia cases with nonreciprocal PML/RARα or RARα-PML fusion genes. Blood 1995; 85: 1169-1174.
37. Grimwade D, Gorman P, Duprez E, Howe K, Langabeer S, Oliver F, Walker H, Culligan D, Waters J, Pomfret M, Goldstone A, Burnett A, Freemont P, Sheer D, Solomon E. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood 1997; 90: 4876-4885.
38. Arnould C, Philippe C, Bourdon V, Grégoire MJ, Berger R, Jonveaux P. The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor α in acute promyelocytic-like leukemia. Hum Mol Genet 1999; 8: 1741-1749.
39. Chen S-J, Zelent A, Tong J-H, Yu H-Q, Wang Z-Y, Derré J, Berger R, Waxman S, Chen Z. Rearrangements of the retinoic acid receptor α and promyelocytic zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukaemia. J Clin Invest 1993; 91: 2260-2267.
40. Chen Z, Brand NJ, Chen A, Chen S-J, Tong J-H, Wang Z-Y, Waxman S, Zelent A. Fusion between a novel Kruppel-like zinc finger gene and the retinoic acid receptor-α locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J 1993; 12: 1161-1167.
41. Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood 1996; 87: 882-886.
42. Wells RA, Catzavelos C, Kamel-Reid S. Fusion of retinoic acid receptor α to NUMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nature Genet 1997; 17: 109-113.
43. Licht JD, Chomienne C, Goy A, Chen A, Scott AA, Head DR, Michaux JL, Wu Y, DeBlasio A, Miller WH, Zelenetz AD, Willman CL, Chen Z, Chen S-J, Zelent A, Macintyre E, Veil A, Cortes J, Kantarjian H, Waxman S. Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17). Blood 1995; 85: 1083-1094.
44. Koken MH, Daniel MT, Gianni M, Zelent A, Licht J, Buzyn A, Minard P, Degos L, Varet B, de Thé H. Retinoic acid, but not arsenic trioxide, degrades the PLZF/RARα fusion protein, without inducing terminal differentiation or apoptosis, in a RA-therapy resistant t(11;17)(q23;q21) APL patient. Oncogene 1999; 18: 1113-1118.
45. Lin RJ, Sternsdorf T, Tini M, Evans RM. Transcriptional regulation in acute promyelocytic leukemia. Oncogene 2001; 20: 7204-7215.
46. Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 2002; 295: 1079-1082.
47. Melnick A, Licht JD. Deconstructing a disease: RARα, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999; 93: 3167-3215.
48. Jansen JH, de Ridder MC, Geertsma WM, Erpelinck CA, van Lom K, Smit EM, Slater R, van der Reijden BA, de Greef GE, Sonneveld P, Lowenberg B. Complete remission of t(11;17) positive acute promyelocytic leukemia induced by all-trans retinoic acid and granulocyte colony-stimulating factor. Blood 1999; 94: 39-45.
49. Petti MC, Fazi F, Gentile M, Diverio D, de Fabritiis P, de Propris MS, Fiorini R, Aloe Spiriti MA, Padula F, Pelicci PG, Nervi C, Lo Coco F. Complete remission through blast cell differentiation in PLZF/RARα-positive acute promyelocytic leukemia: in vitro and in vivo studies. Blood 2002; 100: 1065-1067.
50. Guidez F, Altucci L, Xu K, Rossin A, Wilhelm E, Culligan DJ, Solomon E, Gronemeyer H, Zelent A, Grimwade D. Rexinoid therapy bypasses the differentiation block associated with acute promyelocytic leukemia harboring the PLZF/RARα rearrangement. Blood 2001; 98 (Suppl. 1): 766a (Abstr.).
51. Redner RL, Wang J, Liu JM. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood 1999; 94: 417-428.
52. Kitamura K, Hoshi S, Koike M, Kiyoi H, Saito H, Naoe T. Histone deacetylase inhibitor but not arsenic trioxide differentiates acute promyelocytic leukaemia cells with t(11;17) in combination with all-trans retinoic acid. Br J Haematol 2000; 108: 696-702.
53. Warrell RP, He L-Z, Ricon V, Calleja E, Pandolfi PP. Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Natl Cancer Inst 1998; 90: 1621-1625.
54. Sainty D, Liso V, Cantù-Rajnoldi A, Head D, Mozziconacci M-J, Arnoulet C, Benattar L, Fenu S, Mancini M, Delabesse E, Duchayne E, Mahon F-X, Gutierrez N, Birg F, Biondi A, Grimwade D, Lafage-Pochitaloff M, Hagemeijer A, Flandrin G. A new morphological classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF-RARα rearrangements. Blood 2000; 96: 1287-1296.
55. Grimwade D. The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. Baillière's Best Pract Res Clin Haematol 2001; 14: 497-529.
56. Grimwade D. The pathogenesis of acute promyelocytic leukaemia: evaluation of the role of molecular diagnosis and monitoring in the management of the disease. Br J Haematol 1999; 106: 591-613.
57. Berger R, Bernheim A, Daniel MT, Valensi F, Flandrin G. Karyotype and cell phenotypes in primary acute leukemias. Blood Cells 1981; 7: 287-292.
58. Diverio D, Riccioni R, Pistilli A, Buffolino S, Avvisati G, Mandelli F, Lo Coco F. Improved rapid detection of the pml/rar-alpha fusion gene in acute promyelocytic leukemia. Leukemia 1996; 10: 1214-1216.
59. Gallagher RE, Li Y-P, Rao S, Paietta E, Andersen J, Etkind P, Bennett JM, Tallman MS, Wiernik PH. Characterization of acute promyelocytic leukemia cases with PML-RARα break/fusion sites in PML exon 6: identification of a subgroup with decreased in vitro responsiveness to all-trans retinoic acid. Blood 1995; 86: 1540-1547.
60. Gallagher RE, Willman CL, Slack JL, Andersen JW, Li Y, Viswanatha D, Bloomfield CD, Appelbaum FR, Schiffer CA, Tallman MS, Wiernik PH. Association of PML-RARA fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: an Intergroup molecular study. Blood 1997; 90: 1656-1663.
61. Guglielmi C, Martelli MP, Diverio D, Fenu S, Vegna ML, Cantù-Rajnoldi A, Biondi A, Cocito MG, Del Vecchio L, Tabilio A, Avvisati G, Basso G, Lo Coco F. Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases. Br J Haematol 1998; 102: 1035-1041.
62. Slack JL, Yu M. Constitutive expression of the promyelocytic leukemia-associated oncogene PML-RARα in TF1 cells: isoform-specific and retinoic acid-dependent effects on growth, bcl-2 expression, and apoptosis. Blood 1998; 91: 3347-3356.
63. Borrow J, Goddard AD, Gibbons B, Katz F, Swirsky D, Fioretos T, Dube I, Winfield DA, Kingston J, Hagemeijer A, Rees JKH, Lister TA, Solomon E. Diagnosis of acute promyelocytic leukaemia by RT-PCR: detection of PML-RARA and RARA-PML fusion transcripts. Br J Haematol 1992; 82: 529-540.
64. Vahdat L, Maslak P, Miller WH, Eardley A, Heller G, Scheinberg DA, Warrell RP. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PML-RAR-α isoform, and CD13 expression in patients treated with All-trans retinoic acid. Blood 1994; 84: 3843-3849.
65. Jurcic JG, Nimer SD, Scheinberg DA, DeBlasio T, Warrell RP, Miller WH. Prognostic significance of minimal residual disease detection and PML/RARα isoform type: long-term follow-up in acute promyelocytic leukemia. Blood 2001; 98: 2651-2656.
66. Cassinat B, Chevret S, Zassadowski F, Balitrand N, Guillemot I, Menot M-L, Degos L, Fenaux P, Chomienne C. In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome. Blood 2001; 98: 2862-2864.
67. Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Ceeri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F. Molecular remission in PML/RARα-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood 1997; 90: 1014-1021.
68. Sanz MA, Lo Coco F, Martín G, Avvisati G, Rayón C, Barbui T, Díaz-Mediavilla J, Fioritoni G, González JD, Liso V, Esteve J, Ferrara F, Bolufer P, Bernasconi C, Gonzalez M, Rodeghiero, F, Colomer D, Petti MC, Ribera JM, Mandelli F. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 2000; 96: 1247-1253.
69. Reiter A, Saussele S, Lengfelder E, Weisser A, Reichert A, Hochhaus A, Willer A, Bchner T, Hehlmann R, Cross NCP. Evidence for a DNA damage repair mechanism in the origin of the t(15;17) in acute promyelocytic leukemia (APL). Blood 2000; 96 (Suppl. 1): 694a (Abstr.).
70. Grimwade D. The significance of minimal residual disease in patients with t(15;17). Baillière's Best Pract Res Clin Haematol 2002; 15: 137-158.
71. Li Y-P, Andersen J, Zelent A, Rao S, Paietta E, Tallman MS, Wiernik PH, Gallagher RE. RARα1/RARα2-PML messenger RNA expression in acute promyelocytic leukemia cells - a molecular and laboratory clinical correlative study. Blood 1997; 90: 306-312.
72. Miller WH, Kakizuka A, Frankel SR, Warrell RP, DeBlasio A, Levine K, Evans R, Dmitrovsky E. Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor α clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia. Proc Natl Acad Sci USA 1992; 89: 2694-2698.
73. Grimwade D. Screening for core binding factor gene rearrangements in acute myeloid leukemia. Leukemia 2002; 16: 964-969.
74. Dyck J, Warrell RP, Evans RM, Miller WH. Rapid diagnosis of acute promyelocytic leukemia by immunohistochemical localization of PML/RAR-α protein. Blood 1995; 86: 862-867.
75. Falini B, Flenghi L, Fagioli M, Lo Coco F, Cordone I, Diverio D, Pasqualucci L, Biondi A, Riganelli D, Orleth A, Liso A, Martelli MF, Pelicci PG, Pileri S. Immunocytochemical diagnosis of acute promyelocytic leukemia (M3) with the monoclonal-antibody PG-M3 (anti-PML). Blood 1997; 90: 4046-4053.
76. Hummel JL, Wells RA, Dube ID, Licht JD, Kamel-Reid S. Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia. Oncogene 1999; 18: 633-641.
77. Redner RL, Corey SJ, Rush EA. Differentiation of t(5;17) variant acute promyelocytic leukemia blasts by all-trans retinoic acid. Leukemia 1997; 11: 1014-1016.
78. Cordell JL, Pulford KA, Bigerna B, Roncador G, Banham A, Colombo E, Pelicci PG, Mason DY, Falini B. Detection of normal and chimeric nucleophosmin in human cells. Blood 1999; 93: 632-642.
79. Aventin A, Mateu R, Martino R, Colomer D, Bordes R. A case of cryptic acute promyelocytic leukemia. Leukemia 1998; 12: 1490-1491.
80. Foley R, Soamboonsrup P, Kouroukis T, Leber B, Carter RF, Sunisloe L, Chorneyko K, Neame PB. PML/RARα APL with undifferentiated morphology and stem cell immunophenotype. Leukemia 1998; 12: 1492-1493.
81. Allford S, Grimwade D, Langabeer S, Duprez E, Saurin A, Chatters S, Walker H, Roberts P, Rogers J, Bain B, Patterson K, McKernan A, Freemont P, Solomon E, Burnett A, Linch D. Identification of the t(15;17) in AML FAB types other than M3: evaluation of the role of molecular screening for the PML-RARα rearrangement in newly diagnosed AML. Br J Haematol 1999; 103: 198-207.
82. Virchis A, Massey E, Butler T, Devaraj P, Wright F, Secker-Walker L, Prentice HG, Mehta AB. Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARα fusion gene formation, relapsing as acute promyelocytic leukaemia M3. Br J Haematol 2001; 114: 551-556.
83. Langabeer SE, Grimwade D, Walker H, Rogers JR, Burnett AK, Goldstone AH, Linch DC. A study to determine whether trisomy 8, deleted 9q and trisomy 22 are markers of cryptic rearrangements of PML/RARα, AML1/ETO and CBFB/MYH11 respectively in acute myeloid leukaemia. Br J Haematol 1998; 101: 338-340.
84. Pallisgaard N, Hokland P, Riishøj DC, Pedersen B, Jørgensen P. Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia. Blood 1998; 92: 574-588.
85. Krauter J, Peter W, Pascheberg U, Heinze B, Bergmann L, Hoelzer D, Lübbert M, Schlimok G, Arnold R, Kirchner H, Port M, Ganser A, Heil G. Detection of karyotypic aberrations in acute myeloblastic leukaemia: a prospective comparison between PCR/FISH and standard cytogenetics in 140 patients with de novo AML. Br J Haematol 1998; 103: 72-78.
86. Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, Omoto E, Akiyama H, Tsubaki K, Saito K, Kuriyama K, Oh H, Kitano K, Miyawaki S, Takeyama K, Yamada O, Nishikawa K, Takahashi M, Matsuda S, Ohtake S, Suzushima H, Emi N, Ohno R. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. J Clin Oncol 1998; 16: 78-85.
87. Murray CK, Estey E, Paietta E, Howard RS, Edenfield WJ, Pierce S, Mann KP, Bolan C, Byrd JC. CD56 expression in acute promyelocytic leukemia: a possible indicator of poor treatment outcome? J Clin Oncol 1999; 17: 293-297.
88. Ferrara F, Morabito F, Martino B, Specchia G, Liso V, Nobile F, Boccuni P, Di Noto R, Pane F, Annunziata M, Schiavone EM, De Simone M, Guglielmi C, Del Vecchio L, Lo Coco F. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans retinoic acid and chemotherapy. J Clin Oncol 2000; 18: 1295-1300.
89. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH, Linch DC. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98: 1752-1759.
90. González M, Barragán E, Bolufer P, Chillón C, Colomer D, Borstein R, Calasanz MJ, Gómez-Casares MT, Villegas A, Marugán I, Román J, Martín G, Rayón C, Debén G, Tormo M, Díaz-Mediavilla J, Esteve J, González-San Miguel J, Rivas C, Pérez-Equiza K, García-Sanz R, Capote FJ, Ribera JM, Arias J, León A, Sanz MA. Pretreatment characteristics and clinical outcome of acute promyelocytic leukaemia patients according to the PML-RARα isoforms: a study of the PETHEMA group. Br J Haematol 2001; 114: 99-103.
91. Miller WH, Levine K, DeBlasio A, Frankel SR, Dmitrovsky E, Warrell RP. Detection of minimal residual disease in acute promyelocytic leukemia by a reverse transcription polymerase chain reaction assay for the PML/RAR-alpha fusion mRNA. Blood 1993; 82: 1689-1694.
92. Fukutani H, Naoe T, Ohno R, Yoshida H, Miyawaki S, Shimazaki C, Miyake T, Nakayama Y, Kobayashi H, Goto S, Takeshita A, Kobayashi S, Kato Y, Shiraishi K, Sasada M, Ohtake S, Murakami H, Kobayashi M, Endo N, Shindo H, Matsushita K, Hasegawa S, Tsuji K, Ueda Y, Tominaga N, Furuya H, Inoue Y, Takeuchi J, Morishita H, Iida H. Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. Leukemia 1995; 9: 1478-1482.
93. Gameiro P, Vieira S, Carrara P, Silva AL, Diamond J, de Sousa AD, Mehta AB, Prentice HG, Guimarães JE, Hoffbrand AV, Foroni L, Parreira A. The PML-RARα transcript in long-term follow-up of acute promyelocytic leukemia patients. Haematologica 2001; 86: 577-585.
94. Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Loffler H, Staib P, Heyll A, Seifarth W, Saussele S, Fonatsch C, Gassmann W, Ludwig WD, Hochhaus A, Beelen D, Aul C, Sauerland MC, Heinecke A, Hehlmann R, Wormann B, Hiddemann W, Buchner T. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. Leukemia 2000; 14: 1362-1370.
95. Diverio D, Rossi V, Avvisati G, De Santis S, Pistilli A, Pane F, Saglio G, Martinelli G, Petti MC, Santoro A, Pelicci PG, Mandelli F, Biondi A, Lo Coco, F. Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARα fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter 'AIDA' trial. Blood 1998; 92: 784-789.
96. Lo Coco F, Diverio D, Pandolfi PP, Biondi A, Rossi V, Avvisati G, Rambaldi A, Arcese W, Petti MC, Meloni G, Mandelli F, Grignani F, Masera G, Barbui T, Pelicci PG. Molecular evaluation of residual disease as a predictor of relapse in acute promyelocytic leukaemia. Lancet 1992; 340: 1437-1438.
97. Grimwade D, Howe K, Langabeer S, Burnett AK, Goldstone A, Solomon E. Minimal residual disease detection in acute promyelocytic leukemia by reverse transcriptase PCR: evaluation of PML-RARα and RARα-PML assessment in patients who ultimately relapse. Leukemia 1996; 10: 61-66.
98. Devaraj PE, Foroni L, Prentice HG, Hoffbrand VA, Secker-Walker LM. Relapse of acute promyelocytic leukemia follows serial negative RT-PCR assays: a cautionary tale. Leukemia Res 1996; 20: 733-737.
99. Seale JRC, Varma S, Swirsky DM, Pandolfi PP, Goldman JM, Cross NCP. Quantification of PML/RARα transcripts in acute promyelocytic leukaemia: Explanation for lack of sensitivity of RT-PCR for the detection of minimal residual disease and induction of the leukaemia-specific mRNA by alpha interferon. Br J Haematol 1996; 95: 95-101.
100. Tobal K, Moore H, Macheta M, Liu Yin JA. Monitoring minimal residual disease and predicting relapse in APL by quantitating PML-RARα transcripts with a sensitive competitive RT-PCR method. Leukemia 2001; 15: 1060-1065.
101. Tobal K, Saunders MJ, Grey MR, Yin JAL. Persistence of RARα-PML fusion mRNA detected by reverse-transcriptase polymerase chain reaction in patients in long term remission of acute promyelocytic leukaemia. Br J Haematol 1995; 90: 615-618.
102. Bolufer P, Barragán E, Sanz MA, Martin G, Lerma E, Afan de Ribera E. Monitoring of minimal residual disease with the combined detection of PML/RAR alpha and RAR alpha/PML rearrangements in acute promyelocytic leukemia. Med Clin (Barc) 2000; 114: 281-285.
103. Tobal K, Yin JAL. RT-PCR method with increased sensitivity shows persistence of PML-RARα fusion transcripts in patients in long-term remission of APL. Leukemia 1998; 12: 1349-1354.
104. Nucifora G, Larson RA, Rowley JD. Persistence of the 8;21 translocation in patients with acute myeloid leukemia type M2 in long-term remission. Blood 1993; 82: 712-715.
105. Miyamoto T, Weissman IL, Akashi K. AML1/ETO-expressing non-leukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 2000; 97: 7521-7526.
106. Tobal K, Newton J, Macheta M, Chang J, Morgenstern G, Evans PA, Morgan G, Lucas GS, Yin JAL. Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse. Blood 2000; 95: 815-819.
107. Szczepanski T, Flohr T, Van der Velden VHJ, Bartram CR, van Dongen JJM. Molecular monitoring of residual disease using antigen receptor genes in childhood acute lymphoblastic leukaemia. Baillière's Best Pract Res Clin Haematol 2002; 15: 37-58.
108. San-Miguel JF, Vidriales MB, López-Berges MC, Díaz-Mediavilla J, Gutiérrez N, Cañizo C, Ramos F, Calmuntia MJ, Pérez JJ, González M, Orfao A. Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk-groups and may contribute to post-induction treatment stratification. Blood 2001; 98: 1746-1751.
109. Lo Coco F, Diverio D, Avvisati G, Petti MC, Meloni G, Pogliani EM, Biondi A, Rossi G, Carlo-Stella C, Selleri C, Martino B, Specchia G, Mandelli F. Therapy of molecular relapse in acute promyelocytic leukemia. Blood 1999; 94: 2225-2229.
110. Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Petti MC, Mandelli F, Lo Coco F. Autologous bone-marrow transplantation for acute promyelocytic leukemia in 2nd remission - prognostic relevance of pretransplant minimal residual disease assessment by reverse-transcription polymerase chain reaction of the PML/RARα fusion gene. Blood 1997; 90: 1321-1325.
111. Sanz MA, de la Rubia J, Bonanad S, Barragán E, Sempere A, Martín G, Martinez JA, Jiménez C, Cervera J, Bolufer P, Sanz GF. Prolonged molecular remission after PML/RARα-positive autologous peripheral blood stem cell transplantation in acute promyelocytic leukemia: is relevant pretransplant minimal residual disease in the graft? Leukemia 1998; 12: 992-995.
112. Thomas X, Dombret H, Cordonnier C, Pigneux A, Gardin C, Guerci A, Vekhoff A, Sadoun A, Stamatoullas A, Fegueux N, Maloisel F, Cahn JY, Reman O, Gratecos N, Berthou C, Huguet F, Kotoucek P, Travade P, Buzyn A, de Revel T, Vilque JP, Naccache P, Chomienne C, Degos L, Fenaux P. Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid followed by timed sequential chemotherapy and stem cell transplantation. Leukemia 2000; 14: 1006-1013.
113. Takatsuki H, Umemura T, Sadamura S, Yamashita S, Goto T, Abe Y, Yufu Y, Inaba S, Nishimura J, Nawata H. Detection of minimal residual disease by reverse transcriptase polymerase chain reaction for the PML/RARα fusion mRNA: a study in patients with acute promyelocytic leukemia following peripheral stem cell transplantation. Leukemia 1995; 9: 889-892.
114. Román J, Martín C, Torres A, Jiménez MA, Andrés O, Flores R, de la Torre MJ, Sánchez J, Serrano J
115. Diverio D, Pandolfi PP, Biondi A, Avvisati G, Petti MC, Mandelli F, Pelicci PG, Lo Coco F. Absence of reverse transcription-polymerase chain reaction detectable residual disease in patients with acute promyelocytic leukemia in long-term remission. Blood 1993; 82: 3556-3559.
116. Perego RA, Marenco P, Bianchi C, Cairoli R, Urbano M, Nosari AM, Muti G, Morra E, Del Monte U. PML/RARα transcripts monitored by polymerase chain reaction in acute promyelocytic leukemia during complete remission, relapse and after bone marrow transplantation. Leukemia 1996; 10: 207-212.
117. Grimwade D, Jamal R, Goulden N, Kempski H, Mastrangelo S, Veys P. Salvage of patients with acute promyelocytic leukaemia with residual disease following ABMT performed in second complete remission using all-trans retinoic acid. Br J Haematol 1998; 103: 559-562.
118. Niu C, Yan H, Yu T, Sun H-P, Liu J-X, Li X-S, Wu W, Zhang F-Q, Chen Y, Zhou L, Li J-M, Zeng X-Y, Ou Yang R-R, Yuan M-M, Ren M-Y, Gu F-Y, Cao Q, Gu B-W, Su X-Y, Chen G-Q, Xiong S-M, Zhang T-D, Waxman S, Wang Z-Y, Chen Z, Hu J, Shen Z-X, Chen S-J. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 1999; 94: 3315-3324.
119. Jurcic JG, Caron PC, Miller WH, Yao T-J, Maslak P, Finn RD, Larson SM, Warrell RP, Scheinberg DA. Sequential targeted therapy for relapsed acute promyelocytic leukemia with all-trans retinoic acid and anti-CD33 monoclonal antibody M-195. Leukemia 1995; 9: 244-248.
120. Jurcic JG, DeBlasio T, Dumont L, Yao T-J, Scheinberg DA. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM 195 in acute promyelocytic leukemia. Clin Cancer Res 2000; 6: 372-380.
121. Jurcic JG. Antibody therapy for residual disease in acute myelogenous leukemia. Clin Rev Oncol Hematol 2001; 38: 37-45.
122. Petti MC, Pinazzi MB, Diverio D, Romano A, Petrucci MT, De Santis S, Meloni G, Tafuri A, Mandelli F, Lo Coco F. Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676). Br J Haematol 2001; 115: 63-65.
123. Estey EH, Giles FJ, Kantarjian H, O'Brien S, Cortes J, Freireich FJ, Lopez-Berenstein G, Keating M. Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia. Blood 1999; 94: 2230-2235.
124. Ding W, Li YP, Nobile LM, Grills G, Carrera I, Paietta E, Tallman MS, Wiernik PH, Gallagher RE. Leukemic cellular retinoic acid resistance and missense mutations in the PML-RARα fusion gene after relapse of acute promyelocytic leukemia from treatment with all-trans retinoic acid and intensive chemotherapy. Blood 1998; 92: 1172-1183.
125. Imaizumi M, Suzuki H, Yoshinari M, Sato A, Saito T, Sugawara A, Tsuchiya S, Hatae Y, Fujimoto T, Kakizuka A, Konno T, Iinuma K. Mutations in the E-domain of RARα portion of the PML/RARα chimeric gene may confer clinical resistance to all-trans retinoic acid in acute promyelocytic leukemia. Blood 1998; 92: 374-382.
126. Ct̂é S, Zhou D, Bianchini A, Nervi C, Gallagher RE, Miller WH. Altered ligand binding and transcriptional regulation by mutations in the PML/RARα ligand-binding domain arising in retinoic acid-resistant patients with acute promyelocytic leukemia. Blood 2000; 96: 3200-3208.
127. Zhou DC, Kim SH, Ding W, Schultz C, Warrell RP, Gallagher RE. Frequent mutations in the ligand-binding domain of PML-RARα after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-trans retinoic acid and histone deacetylase inhibitors in vitro and in vivo. Blood 2002; 99: 1356-1363.
128. Gabert J, Beillard E, Bi W, Pallisgaard, N, Gottardi E., Cazzaniga G, Barbany G, Cavé H, Cayuela JM, Grimwade D, Aerts J, van der Velden V, Pane F, Saglio G, van Dongen JJM. European standardisation and quality control program of real time quantitative RT-PCR analysis of fusion gene transcripts for minimal residual disease detection in leukemia patients. Blood 2000; 96 (Suppl. 1): 311a (Abstr.).
129. Slack JL, Bi W, Livak KJ, Beaubier N, Yu M, Clark M, Kim SH, Gallagher RE, Willman CL. Pre-clinical validation of a novel, highly sensitive assay to detect PML-RARα mRNA using real-time reverse-transcription polymerase chain reaction. J Mol Diagn 2001; 3: 141-149.
130. Cassinat B, Zassadowski F, Balitrand N, Barbey C, Rain JD, Fenaux P, Degos L, Vidaud M, Chomienne C. Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR. Leukemia 2000; 14: 324-328.
131. Visani G, Buonamici S, Malagola M, Isidori A, Piccaluga PP, Martinelli G, Ottaviani E, Grafone T, Baccarani M, Tura S. Pulsed ATRA as single therapy restores long-term remission in PML-RARα positive acute promyelocytic leukemia patients: real time quantification of minimal residual disease. A pilot study. Leukemia 2000; 15: 1696-1700.
132. Mitterbauer A, Mannhalter C, Jäger U, Kalhs P, Lechner K, Mitterbauer G. Quantification of minimal residual disease in patients with acute promyelocytic leukemia (APL) by real time quantitative RT-PCR with specific fluorescent hybridization probes. Blood 2000; 94 (Suppl. 1): 313a (Abstr.).
133. Grimwade D, Diverio D, Harrison G, Wheatley K, Rogers J, Lo Coco F, Goldstone AH, Solomon E, Burnett AK. Detection of minimal residual disease (MRD) in APL by 'real-time' RT-PCR: analysis of cases entered into the UK MRC ATRA trial. Blood 1999; 94 (Suppl. 1): 625a (Abstr.).
134. Kwong YL, Au WY, Chim CS, Pang A, Suen C, Liang R. Arsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukemia: clinicopathological and molecular features of a pilot study. Am J Hematol 2001; 66: 274-279.
135. Liu Yin JA. Minimal residual disease in acute myeloid leukaemia. Baillière's Best Pract Res Clin Haematol 2002; 15: 119-135.
136. Buonamici S, Ottaviani E, Testoni N, Montefusco V, Visani G, Bonifazi F, Amabile M, Terragna C, Ruggeri D, Piccaluga PP, Isidori A, Malagola M, Baccarani M, Tura S, Martinelli G. Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state. Blood 2002; 99: 443-449.
137. Guerrasio A, Pilatrino C, De Micheli D, Cilloni D, Serra A, Gottardi E, Parziale A, Marmont F, Diverio D, Divona M, Lo Coco F, Saglio G. Assessment of minimal residual disease (MRD) in CBFbeta/MYH11-positive acute myeloid leukemias by qualitative and quantitative RT-PCR amplification of fusion transcripts. Leukemia 2002; 16: 1176-1181.
138. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, Asou N, Kuriyama K, Jinnai I, Shimazaki C, Akiyama H, Saito K, Oh H, Motoji T, Omoto E, Saito H, Ohno R, Ueda R. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood 1999; 93: 3074-3080.
139. Naoe T, Kiyoi H, Yamamoto Y, Minami Y, Yamamoto K, Ueda R, Saito H. FLT3 tyrosine kinase as a target molecule for selective antileukemia therapy. Cancer Chemother Pharmacol 2001; 48 (Suppl. 1): S27-S30.
140. Druker BJ, Lydon NB. Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000; 105: 3-7.
141. Dash A, Gilliland DG. Molecular genetics of acute myeloid leukaemia. Baillière's Best Pract Res Clin Haematol 2001; 14: 49-64.
142. Chomienne C on behalf of European Retinoic Group. RT-PCR in acute promyelocytic leukemia: second workshop of the European Retinoic Group. Leukemia 1996; 10: 368-371.
143. Bolufer P, Barragń E, Sánz MA, Martín G, Bornstein R, Colomer D, Delgado MD, González M, Marugan I, Román J, Gómez MT, Anguita E, Diverio D, Chomienne C, Briz M. Preliminary experience in external quality control of RT-PCR PML-RARα detection in promyelocytic leukemia. Leukemia 1998; 12: 2024-2028.
144. Bolufer P, Lo Coco F, Grimwade D, Barragán E, Diverio D, Cassinat B, Chomienne C, Gonzalez M, Colomer D, Gomez D, Marugan I, Román J, Delgado MD, García-Marco JA, Bornstein R, Vizmanos JL, Martinez B, Jansen J, Villegas A, de Blas JM, Cabello P, Sanz MA. Variability in the levels of PML-RARα fusion transcripts detected by the laboratories participating in an external quality control program using several reverse transcription polymerase chain reaction protocols. Haematologica 2001; 86: 570-576.
145. Xu L, Zhao WL, Xiong SM, Su XY, Zhao M, Wang C, Gao YR, Niu C, Cao Q, Gu BW, Zhu YM, Gu J, Hu J, Yan H, Shen ZX, Chen Z, Chen SJ. Molecular cytogenetic characterization and clinical relevance of additional complex and/or variant chromosome abnormalities in acute promyelocytic leukemia. Leukemia 2001; 15: 1359-1368.
146. Lo Coco F, De Santis S, Esposito A, Divona M, Diverio D. Molecular monitoring of hematologic malignancies: current and future issues. Semin Hematol 2002; 39 (Suppl. 1): 14-17.