Acute Myeloid Leukemia (AML)

Exploring dysfunctional pathways, mechanisms, and biomarkers in AML to discover new insights into the progression of the disease.


About 190,000 cases of AML are diagnosed globally each year.1


About 147,000 persons will die from AML globally each year.1

Incidence & Mortality

AML is the most common acute leukemia diagnosed in adults and the leading cause of leukemia deaths in the US and globally.

  • An estimated 21,380 persons in the US will be diagnosed during 2017, and 10,590 persons will die from the disease.3
  • 5-year survival rates (~27%) have not significantly improved in the past 15 years.2

AML is generally a disease of older people and is uncommon before the age of 45.2

  • 83.5% of cases in the US are diagnosed in persons older than 44 years.
  • The median age at diagnosis is 68 years.

AML is an aggressive, fast-growing, molecularly and clinically heterogeneous disease characterized by the rapid proliferation of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues that can result in the suppression of normal hematopoiesis.4-6

AML is a clonal malignancy that can develop de novo, as a secondary malignancy (t-AML) following cytotoxic therapy (including alkylating agents, topoisomerase inhibitors, and antimetabolites, and/or myeloablative radio-chemotherapy), or secondary to myelodysplastic syndromes (MDS).4,7

  • Both de novo and secondary AML develop through a multistep process that involves the acquisition of a multiple variety of genetic alterations.6,8
  • Genetic alterations and abnormalities contribute to AML pathogenesis due to their effects on tumor suppressor genes and the dysregulation of intracellular signaling pathways, apoptosis, epigenetic mechanisms, and mitochondrial metabolism.6,8,9

A diagnosis of AML is made based on the presence of 20% or more blasts in the bone marrow or peripheral blood and is further defined by cytogenetic and molecular genetic changes.4

Expanded understanding of the molecular pathogenesis of AML has led to the identification of diagnostic and prognostic markers.4,10

  • Chromosomal abnormalities5,11,12
    • Favorable
      • Abnormalities of chromosome 16 at bands p13 and q22 [t(16;16)(p13;q22) or inv(16)(p13q22)]
      • Translocation between chromosomes 8 and 21 [t(8;21)]
      • Translocation between chromosomes 15 and 17 [t(15;17)]
    • Intermediate
      • Translocation between chromosomes 9 and 11 [t(9;11)] with otherwise normal chromosomes
      • Normal cytogenetics
    • Unfavorable
      • Extra copies of chromosomes 8 or 13 [for example, trisomy 8 (+8)]
      • Deletion of all or part of chromosomes 5 or 7
      • Complex changes on many chromosomes
      • Changes to chromosome 3 at band q26
      • Abnormalities of chromosome 11 at band q23
      • Translocation between chromosomes 6 and 9 [t(6;9)] or 9 and 22 [t(9;22)]
  • Mutations4,11,13
    • Favorable
      • Mutations in the NPM1 or CEBPalpha (biallelic) genes
    • Unfavorable
      • FLT3, RUNX1, ASX11, P53, TET2, or IDH1 or IDH2

The standard therapy for AML has not changed significantly in the past 40 years.6,8

  • Induction therapy with 7+3 combination chemotherapy (7 days of cytarabine and 3 days of an anthracycline)
  • Followed by consolidation therapy to maintain remission (high-dose chemotherapy and allogeneic bone marrow transplant)

Outcomes remain poor, with high rates of relapse for most patients. Older patients pose a difficult therapeutic challenge due to comorbidities and poor performance status, which make them ineligible for intensive therapy.14

Recent additions to the armamentarium are based on cytogenetic or mutation profiles and may only benefit certain patients due to the heterogeneity of the disease.

Dramatic advances in the understanding of AML biology and genetics are being translated into strategies for targeting mutated proteins and dysregulated pathways.

  • The BCL-2 protein is overexpressed in a high proportion of AML cases; elevated levels of BCL-2 correlate with poor prognosis and chemoresistance.15

Relevant Biomarker Pathways

  1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, Barber RM, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3(4):524-548.
  2. Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2014. Bethesda, MD: National Cancer Institute. Published November 2016; updated April 2017. Accessed December 2017.
  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30.
  4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
  5. Leonard JP, Martin P, Roboz GJ. Practical implications of the 2016 revision of the World Health Organization classification of lymphoid and myeloid neoplasms and acute leukemia. J Clin Oncol. 2017;35(23):2708-2715.
  6. Cassier PA, Castets M, Belhabri A, Vey N. Targeting apoptosis in acute myeloid leukaemia. Br J Cancer. 2017;117(8):1089-1098.
  7. Leone G, Pagano L, Ben-Yehuda D, Voso MT. Therapy-related leukemia and myelodysplasia: susceptibility and incidence. Haematologica. 2007;92(10):1389-1398.
  8. Kavanagh S, Murphy T, Law A, et al. Emerging therapies for acute myeloid leukemia: translating biology into the clinic. JCI Insight. 2017 Sep 21;2(18). [Epub ahead of print]
  9. Lim SH, Dubielecka PM, Raghunathan VM. Molecular targeting in acute myeloid leukemia. J Transl Med. 2017;15:183. doi: 10.1186/s12967-017-1281-x.
  10. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-474.
  11. American Society of Clinical Oncology (ASCO). Leukemia - Acute Myeloid - AML: Subtypes. June 2017. Accessed November 15, 2017.
  12. Slovak ML, Kopecky KJ, Cassileth PA, et al; for the Southwest Oncology Group and the Eastern Cooperative Oncology Group. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96(13):4075-4083.
  13. Hou HA, Lin CC, Chou WC, et al. Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia. Leukemia. 2014;28(1):50-58.
  14. Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7.
  15. Campos L, Rouault J-P, Sabido O, et al. High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood. 1993;81(11):3091-3096.
  16. Ghobrial IM, et al. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55(3):178-194.
  17. Pfister SX, Ashworth A. Marked for death: targeting epigenetic changes in cancer. Nat Rev Drug Discov. 2017;16(4):241-263.

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