Current Hematologic Malignancy Reports

, Volume 14, Issue 5, pp 386–394 | Cite as

Acute Myeloid Leukemia: from Mutation Profiling to Treatment Decisions

  • Courtney DiNardoEmail author
  • Curtis Lachowiez
Molecular Testing and Diagnostics (J Khoury, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Molecular Testing and Diagnostics


Purpose of Review

Awareness of the molecular landscape of AML has improved AML care over the last 5 years. This review summarizes updates regarding the diagnostic and therapeutic relevance of key mutations in AML.

Recent Findings

Molecular mutations in genes including NPM1, CEBPA, FLT3, IDH1/2, TP53, RUNX1, and ASXL1 provide important prognostic and/or therapeutic information in AML, including best treatment strategies, transplant recommendations, and significance of MRD detection. Mutational analysis has led to the recognition of new entities including hereditary leukemia syndromes and clonal hematopoiesis of indeterminate potential (CHIP). FLT3 and IDH1/2 mutations are the focus of targeted therapies in the treatment of AML.


Advances in the molecular characterization of AML have provided an improved understanding of leukemogenesis and AML risk stratification, improved disease monitoring techniques, optimized therapeutic strategies, and have led to the development of novel molecular-targeted therapeutics. Ongoing genomic advances will continue to improve upon the outcome of patients with AML.


Acute myeloid leukemia Targeted therapy Minimal residual disease Risk stratification Molecular prognostication 


Compliance with Ethical Standards

Conflict of Interest

Courtney DiNardo reports personal fees from Agios, Abbvie, Celgene, Karyopharm, Medimmune, and Jazz.

Curtis Lachowiez declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review committees of participating sites and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Rai KR, Holland JF, Glidewell OJ, Weinberg V, Brunner K, Obrecht JP, et al. Treatment of acute myelocytic leukemia: a study by cancer and leukemia group B. Blood. 1981;58(6):1203–12.PubMedGoogle Scholar
  2. 2.
    Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53–61.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017; blood-2017.Google Scholar
  4. 4.
    •• DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018; Recently approved (5/3/2019) as first line treatment for patients with IDH1 mutated AML. Important as one of the first targeted therapies other than FLT3 for AML. Google Scholar
  5. 5.
    Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454–64.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Castaigne S, Pautas C, Terré C, Renneville A, Gardin C, Suarez F, Caillot D, Berthon C, Rousselot P, Preudhomme C, Morisset L. Final analysis of the ALFA 0701 study.Google Scholar
  7. 7.
    Schuurhuis GJ, Heuser M, Freeman S, Béné MC, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131(12):1275–91.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Ravandi F, Walter RB, Freeman SD. Evaluating measurable residual disease in acute myeloid leukemia. Blood Adv. 2018;2(11):1356–66.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Konstandin NP, Pastore F, Herold T, Dufour A, Rothenberg-Thurley M, Hinrichsen T, et al. Genetic heterogeneity of cytogenetically normal AML with mutations of CEBPA. Blood Adv. 2018;2(20):2724–31.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Chan SM, Majeti R. Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute myeloid leukemia. Int J Hematol. 2013;98(6):648–57.PubMedPubMedCentralGoogle Scholar
  11. 11.
    •• Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447. Comment: Updated ELN guidelines for incorporation of molecular mutations in diagnosis, prognosis, and therapy of AML. PubMedPubMedCentralGoogle Scholar
  12. 12.
    Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood. 2006;107(10):4011–20.PubMedGoogle Scholar
  13. 13.
    Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254–66.PubMedGoogle Scholar
  14. 14.
    Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Görlich D, Schneider S, Konstandin NP, Dufour A, Bräundl K, Ksienzyk B. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016 :blood-2016.Google Scholar
  15. 15.
    Yang L, Rau R, Goodell MA. DNMT3A in haematological malignancies. Nat Rev Cancer. 2015;15(3):152–65.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Heath EM, Chan SM, Minden MD, Murphy T, Shlush LI, Schimmer AD. Biological and clinical consequences of NPM1 mutations in AML. Leukemia. 2017;31(4):798–807.PubMedGoogle Scholar
  17. 17.
    Loghavi S, Zuo Z, Ravandi F, Kantarjian HM, Bueso-Ramos C, Zhang L, et al. Clinical features of de novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations. J Hematol Oncol. 2014;7(1):74.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, et al. Assessment of minimal residual disease in standard-risk AML. N Engl J Med. 2016;374(5):422–33.Google Scholar
  19. 19.
    Li HY, Deng DH, Huang Y, Ye FH, Huang LL, Xiao Q, et al. Favorable prognosis of biallelic CEBPA gene mutations in acute myeloid leukemia patients: a meta-analysis. Eur J Haematol. 2015;94(5):439–48.PubMedGoogle Scholar
  20. 20.
    Wang H, Chu TT, Han SY, Qi JQ, Tang YQ, Qiu HY, et al. FLT3-ITD and CEBPA mutations predict prognosis in acute myeloid leukemia irrespective of hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2018;29.Google Scholar
  21. 21.
    Dufour A, Schneider F, Metzeler KH, Hoster E, Schneider S, Zellmeier E, et al. Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol. 2009;28(4):570–7.PubMedGoogle Scholar
  22. 22.
    Greif PA, Dufour A, Konstandin NP, Ksienzyk B, Zellmeier E, Tizazu B, et al. GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia. Blood. 2012; blood-2012.Google Scholar
  23. 23.
    Mannelli F, Ponziani V, Bencini S, Bonetti MI, Benelli M, Cutini I, et al. CEBPA–double-mutated acute myeloid leukemia displays a unique phenotypic profile: a reliable screening method and insight into biological features. Haematologica. 2017;102(3):529–40.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Stirewalt DL, Kopecky KJ, Meshinchi S, Engel JH, Pogosova-Agadjanyan EL, Linsley J, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood. 2006;107(9):3724–6.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M, et al. Differential impact of allelic ratio and insertion site in FLT3-ITD positive AML with respect to allogeneic hematopoietic stem cell transplantation. Blood. 2014; blood-2014.Google Scholar
  26. 26.
    Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis: presented in part at the 42nd Annual Meeting of the American Society of Hematology, December 1-5, 2000, San Francisco, CA (abstract 2334). Blood. 2002;99(12):4326–35.PubMedGoogle Scholar
  27. 27.
    Fischer T, Stone RM, DeAngelo DJ, Galinsky I, Estey E, Lanza C, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28(28):4339.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Stone RM, Mandrekar S, Sanford BL, Geyer S, Bloomfield CD, Dohner K, Thiede C, Marcucci G, Lo-Coco F, Klisovic RB, Wei A. The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose C consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18–60 with FLT3 mutations (muts): an international prospective randomized (rand) P-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]).Google Scholar
  29. 29.
    Boddu P, Kantarjian H, Borthakur G, Kadia T, Daver N, Pierce S, et al. Co-occurrence of FLT3-TKD and NPM1 mutations defines a highly favorable prognostic AML group. Blood Advances. 2017;1(19):1546–50.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Pratcorona M, Brunet S, Nomdedéu J, Ribera JM, Tormo M, Duarte R, et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood. 2013; blood-2012.Google Scholar
  31. 31.
    Boddu PC, Kadia TM, Garcia-Manero G, Cortes J, Alfayez M, Borthakur G, et al. Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes. Cancer. 2018.Google Scholar
  32. 32.
    Williams AB, Schumacher B. p53 in the DNA-damage-repair process. Cold Spring Harbor Perspect Med. 2016;5:a026070.Google Scholar
  33. 33.
    Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2(1):a001008.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Peng J, Tang G, et al. TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. J Hematol Oncol. 2015;8(1):45.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Zhang L, McGraw KL, Sallman DA, List AF. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications. Leuk Lymphoma. 2017;58(8):1777–90.PubMedGoogle Scholar
  36. 36.
    Kadia TM, Jain P, Ravandi F, Garcia-Manero G, Andreef M, Takahashi K, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016;122(22):3484–91.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Schoch C, Kern W, Kohlmann A, Hiddemann W, Schnittger S, Haferlach T. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosom Cancer. 2005;43(3):227–38.PubMedGoogle Scholar
  38. 38.
    Ciurea SO, Chilkulwar A, Saliba RM, Chen J, Rondon G, Patel KP, et al. Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations. Blood. 2018;131(26):2989–92.PubMedGoogle Scholar
  39. 39.
    Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023–36.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Sallman DA, DeZern AE, Steensma DP, Sweet KL, Cluzeau T, Sekeres MA, Garcia-Manero G, Roboz GJ, McLemore AF, McGraw KL, Puskas J. Phase 1b/2 combination study of APR-246 and azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).Google Scholar
  41. 41.
    DiNardo CD, Routbort MJ, Bannon SA, Benton CB, Takahashi K, Kornblau SM, et al. Improving the detection of patients with inherited predispositions to hematologic malignancies using next-generation sequencing-based leukemia prognostication panels. Cancer. 2018.Google Scholar
  42. 42.
    DiNardo CD, Bannon SA, Routbort M, Franklin A, Mork M, Armanios M, et al. Evaluation of patients and families with concern for predispositions to hematologic malignancies within the Hereditary Hematologic Malignancy Clinic (HHMC). Clin Lymphoma Myeloma Leuk. 2016;16(7):417–28.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Kanagal-Shamanna R, Loghavi S, DiNardo CD, Medeiros LJ, Garcia-Manero G, Jabbour E, Routbort MJ, Luthra R, Bueso-Ramos CE, Khoury JD. Bone marrow pathologic abnormalities in familial platelet disorder with propensity for myeloid malignancy and germline RUNX1 mutation. Haematologica. 2017102(10):1661–1670PubMedPubMedCentralGoogle Scholar
  44. 44.
    Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, et al. Immune Escape of Relapsed AML Cells after Allogeneic Transplantation. N Engl J Med. 2018.Google Scholar
  45. 45.
    Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.Google Scholar
  46. 46.
    Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–21.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506–10.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909–18.PubMedGoogle Scholar
  49. 49.
    Abdelhamid E, Preudhomme C, Helevaut N, Nibourel O, Gardin C, Rousselot P, et al. Minimal residual disease monitoring based on FLT3 internal tandem duplication in adult acute myeloid leukemia. Leuk Res. 2012;36(3):316–23.PubMedGoogle Scholar
  50. 50.
    Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, al Hinai A, Zeilemaker a, Erpelinck-Verschueren CA, Gradowska PL, Meijer R, Cloos J, Biemond BJ. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med 2018;378(13):1189–1199.PubMedGoogle Scholar
  51. 51.
    Sasaki K, Kanagal-Shamanna R, Montalban-Bravo G, Assi R, Naqvi K, Pierola AA, Yilmaz M, Short NJ, Jabbour EJ, Ravandi F, Kadia TM. The impact of clonal hematopoiesis of indeterminate potential on survival in patients with newly diagnosed acute myeloid leukemia.Google Scholar
  52. 52.
    Larrosa-Garcia M, Baer MR. FLT3 inhibitors in acute myeloid leukemia: current status and future directions. Mol Cancer Ther. 2017;16(6):991–1001.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Man CH, Fung TK, Ho C, Han HH, Chow HC, Ma AC, et al. Sorafenib treatment of FLT3-ITD+ acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent non-responsiveness associated with a D835 mutation. Blood. 2012; blood-2011.Google Scholar
  54. 54.
    Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. The lancet oncology. 2015;16(16):1691–9.PubMedGoogle Scholar
  55. 55.
    Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013;31(25):3110–8.PubMedGoogle Scholar
  56. 56.
    Uy GL, Mandrekar SJ, Laumann K, Marcucci G, Zhao W, Levis MJ, et al. A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Advances. 2017;1(5):331–40.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Battipaglia G, Ruggeri A, Massoud R, El Cheikh J, Jestin M, Antar A, et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer. 2017;123(15):2867–74.PubMedGoogle Scholar
  58. 58.
    Chen YB, Li S, Lane AA, Connolly C, Del Rio C, Valles B, et al. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood and Marrow Transplant. 2014;20(12):2042–8.Google Scholar
  59. 59.
    Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT 3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016;175(3):496–504.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124(9):1954–63.PubMedGoogle Scholar
  61. 61.
    Burchert A, Bug G, Finke J, Stelljes M, Rollig C, Wäsch R, Bornhäuser M, Berg T, Lang F, Ehninger G, Serve H. Sorafenib as maintenance therapy post allogeneic stem cell transplantation for FLT3-ITD positive AML: results from the randomized, double-blind, Placebo-Controlled Multicentre Sormain Trial.Google Scholar
  62. 62.
    Cortes J, Perl AE, Döhner H, Kantarjian H, Martinelli G, Kovacsovics T, et al. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. The Lancet Oncology. 2018.Google Scholar
  63. 63.
    Efficacy and Safety of Single-Agent Quizartinib (Q), a Potent and Selective FLT3 Inhibitor (FLT3i), in Patients (pts) with FLT3-Internal Tandem Duplication (FLT3-ITD)–Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Enrolled in the Global, Phase 3, Randomized Controlled Quantum-R Trial.Google Scholar
  64. 64.
    Sengsayadeth SM, Jagasia M, Engelhardt BG, Kassim A, Strickland SA, Goodman S, et al. Allo-SCT for high-risk AML-CR1 in the molecular era: impact of FLT3/ITD outweighs the conventional markers. Bone Marrow Transplant. 2012;47(12):1535–7.PubMedGoogle Scholar
  65. 65.
    Sandmaier BM, Khaled S, Oran B, Gammon G, Trone D, Frankfurt O. Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant. Am J Hematol. 2018;93(2):222–31.PubMedGoogle Scholar
  66. 66.
    Perl AE, Altman JK, Cortes JE, Smith CC, Litzow M, Baer MR, Claxton DF, Erba HP, Gill SC, Goldberg SL, Jurcic JG. Final results of the Chrysalis trial: a first-in-human phase 1/2 dose-escalation, dose-expansion study of gilteritinib (ASP2215) in patients with relapsed/refractory acute myeloid leukemia (R/R AML).Google Scholar
  67. 67.
    Pratz K, Cherry M, Altman JK, Cooper BW, Cruz JC, Jurcic JG, Levis MJ, Lin TL, Perl AE, Podoltsev NA, Schiller GJ. Preliminary results from a phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in subjects with newly diagnosed acute myeloid leukemia (AML).Google Scholar
  68. 68.
    Schiller GJ, Tuttle P, Desai P. Allogeneic hematopoietic stem cell transplantation in FLT3-ITD–positive acute myelogenous leukemia: the role for flt3 tyrosine kinase inhibitors post-transplantation. Biol Blood Marrow Transplant. 2016;22(6):982–90.PubMedGoogle Scholar
  69. 69.
    Levis MJ, Hamadani M, Logan B, Rosales M, Perl AE, Devine SM, Bahceci E, Chen YB. A phase 3, trial of gilteritinib, as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with FLT3-ITD+ AML.Google Scholar
  70. 70.
    Im AP, Sehgal AR, Carroll MP, Smith BD, Tefferi A, Johnson DE, et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia. 2014;28(9):1774–83.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–44.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017;31(2):272–81.PubMedGoogle Scholar
  73. 73.
    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia. Blood1. 2017; blood-2017.Google Scholar
  74. 74.
    Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013;339(6127):1621–5.PubMedGoogle Scholar
  75. 75.
    Watts J, Baer MR, Yang J, Dinner S, Lee S, Seiter K, Prebet T, Schiller GJ, Ferrell PB, Dao KH, Kantarjian HM. Phase 1 study of the IDH1m inhibitor FT-2102 as a single agent in patients with IDH1m acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of LeukemiaUT MD Anderson Cancer CenterHoustonUSA
  2. 2.Division of Cancer MedicineMD Anderson Cancer CenterHoustonUSA

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