Abstract
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells. In AML, the bone marrow makes many immature cells called blasts, which do not mature and cannot fight infections. AML is a heterogeneous neoplasm with several pathological, genetic, and molecular subtypes. Combinations of various doses and schedules of drugs have been the majority of treatment for all types of AMLs in adult patients. However, not all patients have the same response to these treatments, some of which are adverse responses that are potentially life threatening. Because interindividual responses to AML medications can vary considerably, the potential for genetic contributions to variable drug responses is significant. The pharmacogenomics approach tries to find prognostic and predictive biomarkers permitting to identify patients who could benefit from a particular treatment or those exhibiting higher risks of toxicity. Pharmacogenomics is a rapidly improving science with the potential to revolutionize drug discovery/development and offers one possibility for rationalizing therapy/dose selection. It combines many different fields such as genetics, genomics, molecular biology, pharmacology, pharmaceutics, and population biology. This chapter focuses on treatment of AML, genetic and clinical prognostic markers, and recent advances in the field of pharmacogenomics in AML.
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References
Abla N, Chinn LW, Nakamura T, Liu L, Huang CC, Johns SJ, Kawamoto M, Stryke D, Taylor TR, Ferrin TE, Giacomini KM, Kroetz DL (2008) The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene. J Pharmacol Exp Ther 325(3):859–868
Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, Sallan SE, Lander ES, Golub TR, Korsmeyer SJ (2002) MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 30(1):41–47
Austin H, Delzell E, Cole P (1988) Benzene and leukemia. A review of the literature and a risk assessment. Am J Epidemiol 127(3):419–439
Aydin-Sayitoglu M, Hatirnaz O, Erensoy N, Ozbek U (2006) Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias. Am J Hematol 81(3):162–170
Badrul Hisam HR, Ros M, Aziz A, Narazah M (2006) Screening for 3435C>T and 2677G>T/A polymorphisms of multi-drug resistance (MDR1) gene in Malay patients with leukemia. Malays J Biochem Mol Biol 14(1)
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297
Bartsocas CS, Loukopoulos D (1992) Bloom’s syndrome: incidence, age of onset, and types of leukemia in the Bloom’s syndrome registry. In: Bartsocas CS, Loukopoulos D (eds) Genetics in hematologic disorders. Hemisphere, Washington, DC, pp 241–258
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33(4):451–458
Bogason A, Masquelier M, Lafolie P, Skogastierna C, Paul C, Gruber A, Vitols S (2010) Daunorubicin metabolism in leukemic cells isolated from patients with acute myeloid leukemia. Drug Metab Lett 4(4):228–232
Brockmoller J, Cascorbi I, Kerb R, Roots I (1996) Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Cancer Res 56(17):3915–3925
Burcu M, O’Loughlin KL, Ford LA, Baer MR (2008) Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia 22(11):2110–2115
Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD (2002) Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100(13):4325–4336
Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99(24):15524–15529
Chang P, Kang M, Xiao A, Chang J, Feusner J, Buffler P, Wiemels J (2010) FLT3 mutation incidence and timing of origin in a population case series of pediatric leukemia. BMC Cancer 10:513
Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102(39):13944–13949
Davies SM, Robison LL, Buckley JD, Radloff GA, Ross JA, Perentesis JP (2000) Glutathione S-transferase polymorphisms in children with myeloid leukemia: a Children’s Cancer Group study. Cancer Epidemiol Biomarkers Prev 9(6):563–566
Davies SM, Robison LL, Buckley JD, Tjoa T, Woods WG, Radloff GA, Ross JA, Perentesis JP (2001) Glutathione S-transferase polymorphisms and outcome of chemotherapy in childhood acute myeloid leukemia. J Clin Oncol 19(5):1279–1287
De Jonge HJ, Valk PJ, Veeger NJ, ter Elst A, den Boer ML, Cloos J, de Haas V, van den Heuvel-Eibrink MM, Kaspers GJ, Zwaan CM, Kamps WA, Lowenberg B, de Bont ES (2010) High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia. Blood 116(10):1747–1754
Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A, Bullinger L, Frohling S, Dohner H (2005) Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood 106(12):3740–3746
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3):453–474
Dubinsky MC, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT, Targan SR, Vasiliauskas EA (2002) 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 122(4):904–915
Eisele L, Klein-Hitpass L, Chatzimanolis N, Opalka B, Boes T, Seeber S, Moritz T, Flasshove M (2007) Differential expression of drug-resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia. Acta Haematol 117(1):8–15
Estey E, Dohner H (2006) Acute myeloid leukaemia. Lancet 368(9550):1894–1907
Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286(5439):487–491
Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352(3):254–266
Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS (2005) Post-transcriptional gene silencing by siRNAs and miRNAs. Curr Opin Struct Biol 15(3):331–341
Foran JM (2010) New prognostic markers in acute myeloid leukemia: perspective from the clinic. Hematology Am Soc Hematol Educ Program 2010:47–55
Galmarini CM, Thomas X, Calvo F, Rousselot P, El Jafaari A, Cros E, Dumontet C (2002) Potential mechanisms of resistance to cytarabine in AML patients. Leuk Res 26(7):621–629
Gradhand U, Kim RB (2008) Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2). Drug Metab Rev 40(2):317–354
Green H, Falk IJ, Lotfi K, Paul E, Hermansson M, Rosenquist R, Paul C, Nahi H (2012) Association of ABCB1 polymorphisms with survival and in vitro cytotoxicity in de novo acute myeloid leukemia with normal karyotype. Pharmacogenomics J 12(2):111–118
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A (1998) The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 92(7):2322–2333
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116(3):354–365
Grisendi S, Mecucci C, Falini B, Pandolfi PP (2006) Nucleophosmin and cancer. Nat Rev Cancer 6(7):493–505
Haferlach T, Kohlmann A, Schnittger S, Dugas M, Hiddemann W, Kern W, Schoch C (2005) Global approach to the diagnosis of leukemia using gene expression profiling. Blood 106(4):1189–1198
Haferlach T, Kohlmann A, Wieczorek L, Basso G, Kronnie GT, Bene MC, De Vos J, Hernandez JM, Hofmann WK, Mills KI, Gilkes A, Chiaretti S, Shurtleff SA, Kipps TJ, Rassenti LZ, Yeoh AE, Papenhausen PR, Liu WM, Williams PM, Foa R (2010) Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol 28(15):2529–2537
Hirose M, Hosoi E, Hamano S, Jalili A (2003) Multidrug resistance in hematological malignancy. J Med Invest 50(3–4):126–135
Horwitz M (1997) The genetics of familial leukemia. Leukemia 11(8):1347–1359
Huang Y, Sadee W (2006) Membrane transporters and channels in chemoresistance and -sensitivity of tumor cells. Cancer Lett 239(2):168–182
Illmer T, Schuler US, Thiede C, Schwarz UI, Kim RB, Gotthard S, Freund D, Schakel U, Ehninger G, Schaich M (2002) MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res 62(17):4955–4962
Jordan CT, Guzman ML, Noble M (2006) Cancer stem cells. N Engl J Med 355(12):1253–1261
Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, Tidefelt U, Wahlin A, Hoglund M (2009) Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 113(18):4179–4187
Kelly LM, Gilliland DG (2002) Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 3:179–198
Kim DH, Park JY, Sohn SK, Lee NY, Suh JS, Lee KB (2006a) The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation. Haematologica 91(6):848–851
Kim DH, Park JY, Sohn SK, Lee NY, Baek JH, Jeon SB, Kim JG, Suh JS, Do YR, Lee KB (2006b) Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia. Int J Cancer 118(9):2195–2201
Kindler T, Lipka DB, Fischer T (2010) FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 116(24):5089–5102
Lane SW, Scadden DT, Gilliland DG (2009) The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood 114(6):1150–1157
Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, Head DR, Weick J, Grever MR, Appelbaum FR, Willman CL (1999) Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 94(3):1086–1099
Leroy H, Roumier C, Huyghe P, Biggio V, Fenaux P, Preudhomme C (2005) CEBPA point mutations in hematological malignancies. Leukemia 19(3):329–334
Levine EG, Bloomfield CD (1992) Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure. Semin Oncol 19(1):47–84
Lindstrom MS (2011) NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011:195209
Liotta L, Petricoin E (2000) Molecular profiling of human cancer. Nat Rev Genet 1(1):48–56
List AF, Spier CS, Grogan TM, Johnson C, Roe DJ, Greer JP, Wolff SN, Broxterman HJ, Scheffer GL, Scheper RJ, Dalton WS (1996) Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. Blood 87(6):2464–2469
Loktionov A, Watson MA, Gunter M, Stebbings WS, Speakman CT, Bingham SA (2001) Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor. Carcinogenesis 22(7):1053–1060
Michael M, Doherty MM (2005) Tumoral drug metabolism: overview and its implications for cancer therapy. J Clin Oncol 23(1):205–229
Miller RW (1971) Deaths from childhood leukemia and solid tumors among twins and other sibs in the United States, 1960–67. J Natl Cancer Inst 46(1):203–209
Mishra PJ, Bertino JR (2009) MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics 10(3):399–416
Mrozek K, Heerema NA, Bloomfield CD (2004) Cyto-genetics in acute leukemia. Blood Rev 18(2):115–136
Mrozek K, Dohner H, Bloomfield CD (2007) Influence of new molecular prognostic markers in patients with karyotypically normal acute myeloid leukemia: recent advances. Curr Opin Hematol 14(2):106–114
Niedzielska E, Chybicka A (2011) Risk of recurrence of acute leukemia in children depending on the polymorphism for TPMT, CYP2C9 and CYP2C19. Onkol Pol 14(2):68–70
Peng Y, Feng Q, Wilk D, Adjei AA, Salavaggione OE, Weinshilboum RM, Yee VC (2008) Structural basis of substrate recognition in thiopurine s-methyltransferase. Biochemistry 47(23):6216–6225
Preudhomme C, Sagot C, Boissel N, Cayuela JM, Tigaud I, de Botton S, Thomas X, Raffoux E, Lamandin C, Castaigne S, Fenaux P, Dombret H (2002) Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood 100(8):2717–2723
Radtke I, Mullighan CG, Ishii M, Su X, Cheng J, Ma J, Ganti R, Cai Z, Goorha S, Pounds SB, Cao X, Obert C, Armstrong J, Zhang J, Song G, Ribeiro RC, Rubnitz JE, Raimondi SC, Shurtleff SA, Downing JR (2009) Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proc Natl Acad Sci U S A 106(31):12944–12949
Relling MV, Dervieux T (2001) Pharmacogenetics and cancer therapy. Nat Rev Cancer 1(2):99–108
Robey RW, Polgar O, Deeken J, To KW, Bates SE (2007) ABCG2: determining its relevance in clinical drug resistance. Cancer Metastasis Rev 26(1):39–57
Robey RW, To KK, Polgar O, Dohse M, Fetsch P, Dean M, Bates SE (2009) ABCG2: a perspective. Adv Drug Deliv Rev 61(1):3–13
Rodriguez-Ariza A, Lopez-Pedrera C, Aranda E, Barbarroja N (2011) VEGF targeted therapy in acute myeloid leukemia. Crit Rev Oncol Hematol 80(2):241–256
Rollinson S, Roddam P, Kane E, Roman E, Cartwright R, Jack A, Morgan GJ (2000) Polymorphic variation within the glutathione S-transferase genes and risk of adult acute leukaemia. Carcinogenesis 21(1):43–47
Rukov JL, Vinther J, Shomron N (2011) Pharmacogenomics genes show varying perceptibility to microRNA regulation. Pharmacogenet Genomics 21(5):251–262
Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES, Altshuler D (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409(6822):928–933
Schnittger S, Kern W, Tschulik C, Weiss T, Dicker F, Falini B, Haferlach C, Haferlach T (2009) Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 114(11):2220–2231
Schramm A, Schulte JH, Klein-Hitpass L, Havers W, Sieverts H, Berwanger B, Christiansen H, Warnat P, Brors B, Eils J, Eils R, Eggert A (2005) Prediction of clinical outcome and biological characterization of neuroblastoma by expression profiling. Oncogene 24(53):7902–7912
Schuetz JD, Connelly MC, Sun D, Paibir SG, Flynn PM, Srinivas RV, Kumar A, Fridland A (1999) MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med 5(9):1048–1051
Shi JY, Shi ZZ, Zhang SJ, Zhu YM, Gu BW, Li G, Bai XT, Gao XD, Hu J, Jin W, Huang W, Chen Z, Chen SJ (2004) Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Pharmacogenetics 14(11):759–768
Smith BD, Levis M, Beran M, Giles F, Kantarjian H, Berg K, Murphy KM, Dauses T, Allebach J, Small D (2004) Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 103(10):3669–3676
Spurdle AB, Webb PM, Purdie DM, Chen X, Green A, Chenevix-Trench G (2001) Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype. Carcinogenesis 22(1):67–72
Stirewalt DL, Radich JP (2003) The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3(9):650–665
Stone RM, De Angelo J, Galinsky I, Estey E, Klimek V, Grandin W, Lebwohl D, Yap A, Cohen P, Fox E, Neuberg D, Clark J, Gilliland DG, Griffin JD (2004) PKC 412 FLT3 inhibitor therapy in AML: results of a phase II trial. Ann Hematol 83(Suppl 1):S89–S90
Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, Ehninger G (2006) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 107(10):4011–4020
van den Heuvel-Eibrink MM, Wiemer EA, de Boevere MJ, van der Holt B, Vossebeld PJ, Pieters R, Sonneveld P (2001) MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia. Blood 97(11):3605–3611
van der Kolk DM, de Vries EG, Koning JA, van den Berg E, Muller M, Vellenga E (1998) Activity and expression of the multidrug resistance proteins MRP1 and MRP2 in acute myeloid leukemia cells, tumor cell lines, and normal hematopoietic CD34+ peripheral blood cells. Clin Cancer Res 4(7):1727–1736
van der Kolk DM, de Vries EG, Muller M, Vellenga E (2002) The role of drug efflux pumps in acute myeloid leukemia. Leuk Lymphoma 43(4):685–701
Van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
Varatharajan S, Abraham A, Zhang W, Shaji RV, Ahmed R, Abraham A, George B, Srivastava A, Chandy M, Mathews V, Balasubramanian P (2012) Carbonyl reductase 1 expression influences daunorubicin metabolism in acute myeloid leukemia. Eur J Clin Pharmacol 68(12):1577–1586
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951
Veuger MJ, Honders MW, Landegent JE, Willemze R, Barge RM (2000) High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia. Blood 96(4):1517–1524
Voso MT, D’Alo F, Putzulu R, Mele L, Scardocci A, Chiusolo P, Latagliata R, Lo-Coco F, Rutella S, Pagano L, Hohaus S, Leone G (2002) Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Blood 100(8):2703–2707
Walter MJ, Payton JE, Ries RE, Shannon WD, Deshmukh H, Zhao Y, Baty J, Heath S, Westervelt P, Watson MA, Tomasson MH, Nagarajan R, O’Gara BP, Bloomfield CD, Mrozek K, Selzer RR, Richmond TA, Kitzman J, Geoghegan J, Eis PS, Maupin R, Fulton RS, McLellan M, Wilson RK, Mardis ER, Link DC, Graubert TA, DiPersio JF, Ley TJ (2009) Acquired copy number alterations in adult acute myeloid leukemia genomes. Proc Natl Acad Sci U S A 106(31):12950–12955
Wang WS, Tzeng CH, Chiou TJ, Liu JH, Hsieh RK, Yen CC, Chen PM (1997) High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin’s lymphoma. Jpn J Clin Oncol 27(3):154–157
Weiss RB (1992) The anthracyclines: will we ever find a better doxorubicin? Semin Oncol 19(6):670–686
Wiernik PH (1997) Leukemias and plasma cell myeloma. Cancer Chemother Biol Response Modif 17:390–407
Wouters BJ, Lowenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R (2009) Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113(13):3088–3091
Yue L, Saikawa Y, Ota K, Tanaka M, Nishimura R, Uehara T, Maeba H, Ito T, Sasaki T, Koizumi S (2003) A functional single-nucleotide polymorphism in the human cytidine deaminase gene contributing to ara-C sensitivity. Pharmacogenetics 13(1):29–38
Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG (1997) Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci U S A 94(2):569–574
Zhong Y, Chen B, Feng J, Cheng L, Li Y, Qian J, Ding J, Gao F, Xia G, Chen N, Lu Z (2010) The associations of Janus kinase-2 (JAK2) A830G polymorphism and the treatment outcomes in patients with acute myeloid leukemia. Leuk Lymphoma 51(6):1115–1120
Zipursky A, Poon A, Doyle J (1992) Leukemia in Down syndrome: a review. Pediatr Hematol Oncol 9(2):139–149
Zorko NA, Bernot KM, Whitman SP, Siebenaler RF, Ahmed EH, Marcucci GG, Yanes DA, McConnell KK, Mao C, Kalu C, Zhang X, Jarjoura D, Dorrance AM, Heerema NA, Lee BH, Huang G, Marcucci G, Caligiuri MA (2012) Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias. Blood 120(5):1130–1136
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Hatipoglu, O.F., Bender, O., Gunduz, E., Gunduz, M. (2013). Pharmacogenomics in Acute Myeloid Leukemia. In: Barh, D., Dhawan, D., Ganguly, N. (eds) Omics for Personalized Medicine. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1184-6_12
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