Therapy-related myeloid neoplasms: Pathobiology and clinical characteristics

British Journal of Pharmacology

Volumn 162, Issue 4, 2011, Pages 792-805

  Sill, H ^a   Olipitz, W ^b   Zebisch, A ^c   Schulz, E ^a   Wolfler A ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

^b Massachusetts Institute of Technology Cambridge   (United States)

^c UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

alkylating agents; antimetabolites; genetic susceptibility; granulocyte colony stimulating factor; ionizing radiation; stem cell transplantation; therapy related acute myeloid leukaemia; therapy related myelodysplastic syndrome; therapy related myeloid neoplasms; topoisomerase II inhibitors

Indexed keywords

ALKYLATING AGENT; ANTINEOPLASTIC ANTIMETABOLITE; AZATHIOPRINE; CAMPTOTHECIN; CARBOPLATIN; CHLORAMBUCIL; CISPLATIN; CLADRIBINE; CYCLOPHOSPHAMIDE; DACARBAZINE; DAUNORUBICIN; DOXORUBICIN; EPIRUBICIN; ETHYLNITROSOUREA; ETOPOSIDE; FLUDARABINE; FLUOROURACIL; GYRASE INHIBITOR; IFOSFAMIDE; LENALIDOMIDE; MELPHALAN; MITOMYCIN C; MITOXANTRONE; PROCARBAZINE; RAZOXANE; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RETINOIC ACID; TEMOZOLOMIDE; TIOGUANINE; UNINDEXED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; BREAST CANCER; CANCER RADIOTHERAPY; CANCER RISK; CANCER SUSCEPTIBILITY; CARCINOGENESIS; CARCINOGENICITY; DOSE RESPONSE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HEMATOLOGIC MALIGNANCY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HODGKIN DISEASE; HUMAN; IONIZING RADIATION; LYMPHOMA; MOLECULARLY TARGETED THERAPY; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; PROMYELOCYTIC LEUKEMIA; REDUCED INTENSITY CONDITIONING; REVIEW; RISK FACTOR; SECOND CANCER; SOMATIC MUTATION;

ANIMALS; ANTINEOPLASTIC AGENTS; GENETIC PREDISPOSITION TO DISEASE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LEUKEMIA, MYELOID, ACUTE; MYELODYSPLASTIC SYNDROMES; NEOPLASMS, SECOND PRIMARY; PROGNOSIS; RADIOTHERAPY;

EID: 79251470793     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.01100.x     Document Type: Review

References (154)

1. Aguilera DG, Vaklavas C, Tsimberidou AM, Wen S, Medeiros LJ, Corey SJ, (2009). Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. J Pediatr Hematol Oncol 31: 803-811.
2. Allan JM, Rabkin CS, (2005). Genetic susceptibility to iatrogenic malignancy. Pharmacogenomics 6: 615-628.
3. Allan JM, Travis LB, (2005). Mechanisms of therapy-related carcinogenesis. Nat Rev Cancer 5: 943-955.
4. Andersen MT, Andersen MK, Christiansen DH, Pedersen-Bjergaard J, (2008). NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features. Leukemia 22: 951-955.
5. Andrieu JM, Ifrah N, Payen C, Fermanian J, Coscas Y, Flandrin G, (1990). Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease. J Clin Oncol 8: 1148-1154.
6. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. (2006). Age and acute myeloid leukemia. Blood 107: 3481-3485.
7. Armand P, Kim HT, DeAngelo DJ, Ho VT, Cutler CS, Stone RM, et al. (2007). Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol Blood Marrow Transplant 13: 655-664.
8. Au WY, Fung AT, Ma ES, Liang RH, Kwong YL, (2004). Low frequency of FLT3 gene internal tandem duplication and activating loop mutation in therapy-related acute myelocyticleukemia and myelodysplastic syndrome. Cancer Genet Cytogenet 149: 169-172.
9. Baron V, Adamson ED, Calogero A, Ragona G, Mercola D, (2006). The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther 13: 115-124.
10. Beaumont M, Sanz M, Carli PM, Maloisel F, Thomas X, Detourmignies L, et al. (2003). Therapy-related acute promyelocytic leukemia. J Clin Oncol 21: 2123-2137.
11. Beekman R, Touw IP, (2010). G-CSF and its receptor in myeloid malignancy. Blood 115: 5131-5136.
12. Ben-Yehuda D, Krichevsky S, Caspi O, Rund D, Polliack A, Abeliovich D, et al. (1996). Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype. Blood 88: 4296-4303.
13. Borthakur G, Lin E, Jain N, Estey EE, Cortes JE, O'Brien S, et al. (2009). Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo core-binding factor leukemia. Cancer 115: 3217-3221.
14. Bougeard G, Sesboue R, Baert-Desurmont S, Vasseur S, Martin C, Tinat J, et al. (2008). Molecular basis of the Li-Fraumeni syndrome: an update from the French LFS families. J Med Genet 45: 535-538.
15. Castilla LH, Wijmenga C, Wang Q, Stacy T, Speck NA, Eckhaus M, et al. (1996). Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell 87: 687-696.
16. Castilla LH, Garrett L, Adya N, Orlic D, Dutra A, Anderson S, et al. (1999). The fusion gene Cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia. Nat Genet 23: 144-146.
17. Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME, et al. (2007). Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood 110: 1379-1387.
18. Chantrain CF, Jijon P, De Raedt T, Vermylen C, Poirel HA, Legius E, et al. (2007). Therapy-related acute myeloid leukemia in a child with Noonan syndrome and clonal duplication of the germline PTPN11 mutation. Pediatr Blood Cancer 48: 101-104.
19. Christiansen DH, Pedersen-Bjergaard J, (2001). Internal tandem duplications of the FLT3 and MLL genes are mainly observed in atypical cases of therapy-related acute myeloid leukemia with a normal karyotype and are unrelated to type of previous therapy. Leukemia 15: 1848-1851.
20. Clark OA, Lyman GH, Castro AA, Clark LG, Djulbegovic B, (2005). Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol 23: 4198-4214.
21. D'Andrea AD, Grompe M, (2003). The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 3: 23-34.
22. Delwail V, Jais JP, Colonna P, Andrieu JM, (2002). Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high-dose irradiation. Br J Haematol 118: 189-194.
23. Denayer E, de Ravel T, Legius E, (2008). Clinical and molecular aspects of RAS related disorders. J Med Genet 45: 695-703.
24. Descatha A, Jenabian A, Conso F, Ameille J, (2005). Occupational exposures and haematological malignancies: overview on human recent data. Cancer Causes Control 16: 939-953.
25. Dissing M, Le Beau MM, Pedersen-Bjergaard J, (1998). Inversion of chromosome 16 and uncommon rearrangements of the CBFB and MYH11 genes in therapy-related acute myeloid leukemia: rare events related to DNA-topoisomerase II inhibitors? J Clin Oncol 16: 1890-1896.
26. Dockhorn-Dworniczak B, Wolff J, Poremba C, Schafer KL, Ritter J, Gullotta F, et al. (1996). A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome. Eur J Cancer 32A: 1359-1365.
27. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. (2010). Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115: 453-474.
28. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, et al. (2004). Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair 3: 1389-1407.
29. Ellis NA, Huo D, Yildiz O, Worrillow LJ, Banerjee M, Le Beau MM, et al. (2008). MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood 112: 741-749.
30. Felix CA, Hosler MR, Provisor D, Salhany K, Sexsmith EA, Slater DJ, et al. (1996). The p53 gene in pediatric therapy-related leukemia and myelodysplasia. Blood 87: 4376-4381.
31. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. (2009). Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10: 223-232.
32. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, et al. (2010). Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 28: 562-569.
33. Fenske TS, McMahon C, Edwin D, Jarvis JC, Cheverud JM, Minn M, et al. (2006). Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice. Cancer Res 66: 5029-5038.
34. Gerson SL, Phillips W, Kastan M, Dumenco LL, Donovan C, (1996). Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU. Blood 88: 1649-1655.
35. Godley LA, Njiaju UO, Green M, Weiner H, Lin S, Odenike O, et al. (2010). Treatment of therapy-related myeloid neoplasms with high-dose cytarabine/mitoxantrone followed by hematopoietic stem cell transplant. Leuk Lymphoma 51: 995-1006.
36. Gonzalez KD, Noltner KA, Buzin CH, Gu D, Wen-Fong CY, Nguyen VQ, et al. (2009). Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol 27: 1250-1256.
37. Gustafson SA, Lin P, Chen SS, Chen L, Abruzzo LV, Luthra R, et al. (2009). Therapy-related acute myeloid leukemia with t(8;21) (q22;q22) shares many features with de novo acute myeloid leukemia with t(8;21)(q22;q22) but does not have a favorable outcome. Am J Clin Pathol 131: 647-655.
38. de Guzman CG, Warren AJ, Zhang Z, Gartland L, Erickson P, Drabkin H, et al. (2002). Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol Cell Biol 22: 5506-5517.
39. Haddy N, Le Deley MC, Samand A, Diallo I, Guerin S, Guibout C, et al. (2006). Role of radiotherapy and chemotherapy in the risk of secondary leukaemia after a solid tumour in childhood. Eur J Cancer 42: 2757-2764.
40. Hartman M, Loy EY, Ku CS, Chia KS, (2010). Molecular epidemiology and its current clinical use in cancer management. Lancet Oncol 11: 383-390.
41. Hasan SK, Mays AN, Ottone T, Ledda A, La Nasa G, Cattaneo C, et al. (2008). Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis. Blood 112: 3383-3390.
42. Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA, (2008). DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8: 193-204.
43. Hershman D, Neugut AI, Jacobson JS, Wang J, Tsai WY, McBride R, et al. (2007). Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 99: 196-205.
44. Higuchi M, O'Brien D, Kumaravelu P, Lenny N, Yeoh EJ, Downing JR, (2002). Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell 1: 63-74.
45. Hisada M, Garber JE, Fung CY, Fraumeni JF, Jr, Li FP, (1998). Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90: 606-611.
46. Horsfall MJ, Gordon AJ, Burns PA, Zielenska M, van der Vliet GM, Glickman BW, (1990). Mutational specificity of alkylating agents and the influence of DNA repair. Environ Mol Mutagen 15: 107-122.
47. Hoyle CF, de Bastos M, Wheatley K, Sherrington PD, Fischer PJ, Rees JK, et al. (1989). AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial. Br J Haematol 72: 45-53.
48. Ioannidis JP, Castaldi P, Evangelou E, (2010). A compendium of genome-wide associations for cancer: critical synopsis and reappraisal. J Natl Cancer Inst 102: 846-858.
49. Jiang Y, Dunbar A, Gondek LP, Mohan S, Rataul M, O'Keefe C, et al. (2009). Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood 113: 1315-1325.
50. Joannides M, Grimwade D, (2010). Molecular biology of therapy-related leukaemias. Clin Transl Oncol 12: 8-14.
51. Joslin JM, Fernald AA, Tennant TR, Davis EM, Kogan SC, Anastasi J, et al. (2007). Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders. Blood 110: 719-726.
52. Kaina B, Christmann M, Naumann S, Roos WP, (2007). MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst) 6: 1079-1099.
53. Kantarjian HM, Estey EH, Keating MJ, (1993). Treatment of therapy-related leukemia and myelodysplastic syndrome. Hematol Oncol Clin North Am 7: 81-107.
54. Kern W, Haferlach T, Schnittger S, Hiddemann W, Schoch C, (2004). Prognosis in therapy-related acute myeloid leukemia and impact of karyotype. J Clin Oncol 22: 2510-2511.
55. Klymenko SV, Bink K, Trott KR, Bebeshko VG, Bazyka DA, Dmytrenko IV, et al. (2005). MLL gene alterations in radiation-associated acute myeloid leukemia. Exp Oncol 27: 71-75.
56. Knight JA, Skol AD, Shinde A, Hastings D, Walgren RA, Shao J, et al. (2009). Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility. Blood 113: 5575-5582.
57. Koenigsmann J, Rudolph C, Sander S, Kershaw O, Gruber AD, Bullinger L, et al. (2009). Nf1 haploinsufficiency and Icsbp deficiency synergize in the development of leukemias. Blood 113: 4690-4701.
58. Kroger N, Brand R, van Biezen A, Cahn JY, Slavin S, Blaise D, et al. (2006). Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant 37: 183-189.
59. Kroger N, Brand R, van Biezen A, Zander A, Dierlamm J, Niederwieser D, et al. (2009). Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation. Haematologica 94: 542-549.
60. Kuderer NM, Dale DC, Crawford J, Lyman GH, (2007). Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 25: 3158-3167.
61. Kuribayashi K, Matsunaga T, Sakai T, Wada Y, Tateno K, Murase K, et al. (2005). A patient with TP53 germline mutation developed Bowen's disease and myelodysplastic syndrome with myelofibrosis after chemotherapy against ovarian cancer. Intern Med 44: 490-495.
62. Kwong YL, (2010). Azathioprine: association with therapy-related myelodysplastic syndrome and acute myeloid leukemia. J Rheumatol 37: 485-490.
63. Kyle RA, Pierre RV, Bayrd ED, (1970). Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med 283: 1121-1125.
64. Kyle RA, Pierre RV, Bayrd ED, (1974). Primary amyloidosis and acute leukemia associated with melphalan therapy. Blood 44: 333-337.
65. Lai F, Godley LA, Joslin J, Fernald AA, Liu J, Espinosa R 3rd, et al. (2001). 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 71: 235-245.
66. Larson RA, Wernli M, Le Beau MM, Daly KM, Pape LH, Rowley JD, et al. (1988). Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine. Blood 72: 1333-1339.
67. Lauchle JO, Braun BS, Loh ML, Shannon K, (2006). Inherited predispositions and hyperactive Ras in myeloid leukemogenesis. Pediatr Blood Cancer 46: 579-585.
68. Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, et al. (2007). Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 25: 292-300.
69. Leleu X, Soumerai J, Roccaro A, Hatjiharissi E, Hunter ZR, Manning R, et al. (2009). Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenstrom macroglobulinemia treated with nucleoside analogs. J Clin Oncol 27: 250-255.
70. Leone G, Mele L, Pulsoni A, Equitani F, Pagano L, (1999). The incidence of secondary leukemias. Haematologica 84: 937-945.
71. Leone G, Fianchi L, Pagano L, Voso MT, (2010). Incidence and susceptibility to therapy-related myeloid neoplasms. Chem Biol Interact 184: 39-45.
72. Levesque JP, Winkler IG, (2008). Mobilization of hematopoietic stem cells: state of the art. Curr Opin Organ Transplant 13: 53-58.
73. Li FP, Fraumeni JF, Jr, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, et al. (1988). A cancer family syndrome in twenty-four kindreds. Cancer Res 48: 5358-5362.
74. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. (2006). Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355: 1456-1465.
75. Little JB, (1993). Cellular, molecular, and carcinogenic effects of radiation. Hematol Oncol Clin North Am 7: 337-352.
76. Litzow MR, Tarima S, Perez WS, Bolwell BJ, Cairo MS, Camitta BM, et al. (2010). Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood 115: 1850-1857.
77. Lyman GH, Dale DC, Wolff DA, Culakova E, Poniewierski MS, Kuderer NM, et al. (2010). Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review. J Clin Oncol 28: 2914-2924.
78. McLeod HL, Krynetski EY, Relling MV, Evans WE, (2000). Genetic polymorphism of thiopurine methyltransferase and its clinical relevance for childhood acute lymphoblastic leukemia. Leukemia 14: 567-572.
79. Mahgoub N, Taylor BR, Le Beau MM, Gratiot M, Carlson KM, Atwater SK, et al. (1999). Myeloid malignancies induced by alkylating agents in Nf1 mice. Blood 93: 3617-3623.
80. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. (2009). Finding the missing heritability of complex diseases. Nature 461: 747-753.
81. Margison GP, Santibanez-Koref MF, (2002). O6-alkylguanine-DNA alkyltransferase: role in carcinogenesis and chemotherapy. Bioessays 24: 255-266.
82. Maris JM, Wiersma SR, Mahgoub N, Thompson P, Geyer RJ, Hurwitz CG, et al. (1997). Monosomy 7 myelodysplastic syndrome and other second malignant neoplasms in children with neurofibromatosis type 1. Cancer 79: 1438-1446.
83. Mauritzson N, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z, et al. (2002). Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia 16: 2366-2378.
84. Mays AN, Osheroff N, Xiao Y, Wiemels JL, Felix CA, Byl JA, et al. (2010). Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia. Blood 115: 326-330.
85. Melchert M, Williams C, List A, (2007). Remitting activity of lenalidomide in treatment-induced myelodysplastic syndrome. Leukemia 21: 1576-1578.
86. Mistry AR, Felix CA, Whitmarsh RJ, Mason A, Reiter A, Cassinat B, et al. (2005). DNA topoisomerase II in therapy-related acute promyelocytic leukemia. N Engl J Med 352: 1529-1538.
87. Morrison VA, Rai KR, Peterson BL, Kolitz JE, Elias L, Appelbaum FR, et al. (2002). Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011. J Clin Oncol 20: 3878-3884.
88. Mullenders L, Atkinson M, Paretzke H, Sabatier L, Bouffler S, (2009). Assessing cancer risks of low-dose radiation. Nat Rev Cancer 9: 596-604.
89. Nitiss JL, (2009). Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer 9: 338-350.
90. Offman J, Opelz G, Doehler B, Cummins D, Halil O, Banner NR, et al. (2004). Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation. Blood 104: 822-828.
91. Ojha RP, Fischbach LA, Zhou Y, Felini MJ, Singh KP, Thertulien R, (2010). Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma. Cancer Epidemiol 34: 274-278.
92. Pagana L, Pulsoni A, Tosti ME, Avvisati G, Mele L, Mele M, et al. (2001). Clinical and biological features of acute myeloid leukaemia occurring as second malignancy: GIMEMA archive of adult acute leukaemia. Br J Haematol 112: 109-117.
93. Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, et al. (2007). Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet 39: 1007-1012.
94. Papageorgio C, Seiter K, Feldman EJ, (1999). Therapy-related myelodysplastic syndrome in adults with neurofibromatosis. Leuk Lymphoma 32: 605-608.
95. Patt DA, Duan Z, Fang S, Hortobagyi GN, Giordano SH, (2007). Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 25: 3871-3876.
96. Pearson TA, Manolio TA, (2008). How to interpret a genome-wide association study. JAMA 299: 1335-1344.
97. Pedersen-Bjergaard J, Daugaard G, Hansen SW, Philip P, Larsen SO, Rorth M, (1991). Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338: 359-363.
98. Pedersen-Bjergaard J, Pedersen M, Roulston D, Philip P, (1995). Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 86: 3542-3552.
99. Perilongo G, Felix CA, Meadows AT, Nowell P, Biegel J, Lange BJ, (1993). Sequential development of Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and myeloid leukemia in a child with type 1 neurofibromatosis: a clinical and cytogenetic case report. Leukemia 7: 912-915.
100. Petronis A, (2010). Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature 465: 721-727.
101. Philip P, Pedersen-Bjergaard J, (1988). Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias. Cancer Genet Cytogenet 31: 227-236.
102. Preston DL, Kusumi S, Tomonaga M, Izumi S, Ron E, Kuramoto A, et al. (1994). Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987. Radiat Res 137 (Suppl. 2): S68-S97.
103. Pugsley MK, Authier S, Curtis MJ, (2008). Principles of safety pharmacology. Br J Pharmacol 154: 1382-1399.
104. Rassool FV, Gaymes TJ, Omidvar N, Brady N, Beurlet S, Pla M, et al. (2007). Reactive oxygen species, DNA damage, and error-prone repair: a model for genomic instability with progression in myeloid leukemia? Cancer Res 67: 8762-8771.
105. Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, et al. (2008). Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 111: 86-93.
106. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al. (2007). Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet 39: 1013-1017.
107. Reimer RR, Hoover R, Fraumeni JF, Jr, Young RC, (1977). Acute leukemia after alkylating-agent therapy of ovarian cancer. N Engl J Med 297: 177-181.
108. Relling MV, Boyett JM, Blanco JG, Raimondi S, Behm FG, Sandlund JT, et al. (2003). Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood 101: 3862-3867.
109. Richardson C, Jasin M, (2000). Frequent chromosomal translocations induced by DNA double-strand breaks. Nature 405: 697-700.
110. Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, et al. (2007). Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet 39: 70-74.
111. Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, et al. (2006). The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 107: 4628-4635.
112. Rosner F, Grunwald H, (1975). Hodgkin's disease and acute leukemia. Report of eight cases and review of the literature. Am J Med 58: 339-353.
113. Rothkamm K, Kuhne M, Jeggo PA, Lobrich M, (2001). Radiation-induced genomic rearrangements formed by nonhomologous end-joining of DNA double-strand breaks. Cancer Res 61: 3886-3893.
114. Rowley JD, Golomb HM, Vardiman JW, (1981). Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood 58: 759-767.
115. Rund D, Krichevsky S, Bar-Cohen S, Goldschmidt N, Kedmi M, Malik E, et al. (2005). Therapy-related leukemia: clinical characteristics and analysis of new molecular risk factors in 96 adult patients. Leukemia 19: 1919-1928.
116. Saffhill R, Margison GP, O'Connor PJ, (1985). Mechanisms of carcinogenesis induced by alkylating agents. Biochim Biophys Acta 823: 111-145.
117. Salzer WL, Devidas M, Carroll WL, Winick N, Pullen J, Hunger SP, et al. (2010). Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the children's oncology group. Leukemia 24: 355-370.
118. Schnittger S, Bacher U, Haferlach C, Kern W, Haferlach T, (2007). Rare CBFB-MYH11 fusion transcripts in AML with inv(16)/t(16;16) are associated with therapy-related AML M4eo, atypical cytomorphology, atypical immunophenotype, atypical additional chromosomal rearrangements and low white blood cell count: a study on 162 patients. Leukemia 21: 725-731.
119. Schoch C, Kern W, Schnittger S, Hiddemann W, Haferlach T, (2004). Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 18: 120-125.
120. Schonfeld SJ, Gilbert ES, Dores GM, Lynch CF, Hodgson DC, Hall P, et al. (2006). Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35 511 patients. J Natl Cancer Inst 98: 215-218.
121. Sebastiani P, Timofeev N, Dworkis DA, Perls TT, Steinberg MH, (2009). Genome-wide association studies and the genetic dissection of complex traits. Am J Hematol 84: 504-515.
122. Seedhouse C, Russell N, (2007). Advances in the understanding of susceptibility to treatment-related acute myeloid leukaemia. Br J Haematol 137: 513-529.
123. Shulman LN, (1993). The biology of alkylating-agent cellular injury. Hematol Oncol Clin North Am 7: 325-335.
124. Side LE, Curtiss NP, Teel K, Kratz C, Wang PW, Larson RA, et al. (2004). RAS, FLT3, and TP53 mutations in therapy-related myeloid malignancies with abnormalities of chromosomes 5 and 7. Genes Chromosomes Cancer 39: 217-223.
125. Sigurdson AJ, Bhatti P, Preston DL, Doody MM, Kampa D, Alexander BH, et al. (2008). Routine diagnostic X-ray examinations and increased frequency of chromosome translocations among U.S. radiologic technologists. Cancer Res 68: 8825-8831.
126. Singh ZN, Huo D, Anastasi J, Smith SM, Karrison T, Le Beau MM, et al. (2007). Therapy-related myelodysplastic syndrome: morphologic subclassification may not be clinically relevant. Am J Clin Pathol 127: 197-205.
127. Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, et al. (2003). Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 102: 43-52.
128. Smith-Bindman R, Lipson J, Marcus R, Kim KP, Mahesh M, Gould R, et al. (2009). Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med 169: 2078-2086.
129. Speicher MR, Geigl JB, Tomlinson IP, (2010). Effect of genome-wide association studies, direct-to-consumer genetic testing, and high-speed sequencing technologies on predictive genetic counselling for cancer risk. Lancet Oncol 11: 890-898.
130. Stiller CA, Chessells JM, Fitchett M, (1994). Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br J Cancer 70: 969-972.
131. Stillman WS, Varella-Garcia M, Irons RD, (2000). The benzene metabolite, hydroquinone, selectively induces 5q31- and -7 in human CD34+CD19- bone marrow cells. Exp Hematol 28: 169-176.
132. Swolin B, Rodjer S, Westin J, (2008). Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature. Ann Hematol 87: 467-474.
133. Sypkens Smit CG, Meyler L, (1970). [A patient with ovarian cancer metastasis cured (?) by cytostatic agents and died from acute myeloid leukemia]. Ned Tijdschr Geneeskd 114: 1620-1623.
134. Takeyama K, Seto M, Uike N, Hamajima N, Ino T, Mikuni C, et al. (2000). Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors. Int J Hematol 71: 144-152.
135. Talwalkar SS, Yin CC, Naeem RC, Hicks MJ, Strong LC, Abruzzo LV, (2010). Myelodysplastic syndromes arising in patients with germline TP53 mutation and Li-Fraumeni syndrome. Arch Pathol Lab Med 134: 1010-1015.
136. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, et al. (2001). Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29: 465-468.
137. Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, et al. (2007). Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol 25: 493-500.
138. Thirman MJ, Larson RA, (1996). Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 10: 293-320.
139. Touw IP, Bontenbal M, (2007). Granulocyte colony-stimulating factor: key (f)actor or innocent bystander in the development of secondary myeloid malignancy? J Natl Cancer Inst 99: 183-186.
140. Travis LB, Andersson M, Gospodarowicz M, van Leeuwen FE, Bergfeldt K, Lynch CF, et al. (2000). Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92: 1165-1171.
141. Treon SP, Branagan AR, Ioakimidis L, Soumerai JD, Patterson CJ, Turnbull B, et al. (2009). Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia. Blood 113: 3673-3678.
142. Trumpp A, Essers M, Wilson A, (2010). Awakening dormant haematopoietic stem cells. Nat Rev Immunol 10: 201-209.
143. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114: 937-951.
144. Visscher PM, Hill WG, Wray NR, (2008). Heritability in the genomics era-concepts and misconceptions. Nat Rev Genet 9: 255-266.
145. Voso MT, D'Alo F, Greco M, Fabiani E, Criscuolo M, Migliara G, et al. (2010). Epigenetic changes in therapy-related MDS/AML. Chem Biol Interact 184: 46-49.
146. Waters TR, Swann PF, (1997). Cytotoxic mechanism of 6-thioguanine: hMutSalpha, the human mismatch binding heterodimer, binds to DNA containing S6-methylthioguanine. Biochemistry 36: 2501-2506.
147. Westendorf JJ, Yamamoto CM, Lenny N, Downing JR, Selsted ME, Hiebert SW, (1998). The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol 18: 322-333.
148. Witherspoon RP, Deeg HJ, Storer B, Anasetti C, Storb R, Appelbaum FR, (2001). Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol 19: 2134-2141.
149. Wölfler A, Danen-van Oorschot AA, Haanstra JR, Valkhof M, Bodner C, Vroegindeweij E, et al. (2010). Lineage-instructive function of C/EBP alpha in multipotent hematopoietic cells and early thymic progenitors. Blood 116: 4116-4125.
150. Woodard P, Barfield R, Hale G, Horwitz E, Leung W, Ribeiro R, et al. (2006). Outcome of hematopoietic stem cell transplantation for pediatric patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome. Pediatr Blood Cancer 47: 931-935.
151. Yakoub-Agha I, de La Salmoniere P, Ribaud P, Sutton L, Wattel E, Kuentz M, et al. (2000). Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol 18: 963-971.
152. Zebisch A, Staber PB, Delavar A, Bodner C, Hiden K, Fischereder K, et al. (2006). Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Cancer Res 66: 3401-3408.
153. Zebisch A, Czernilofsky AP, Keri G, Smigelskaite J, Sill H, Troppmair J, (2007). Signaling through RAS-RAF-MEK-ERK: from basics to bedside. Curr Med Chem 14: 601-623.
154. Zebisch A, Haller M, Hiden K, Goebel T, Hoefler G, Troppmair J, et al. (2009). Loss of RAF kinase inhibitor protein is a somatic event in the pathogenesis of therapy-related acute myeloid leukemias with C-RAF germline mutations. Leukemia 23: 1049-1053.