Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities

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Primary Author(s)*

Dan Wang, Ph.D.

Daynna J. Wolff, Ph.D.

General Disease Overview / Description of Cancer Category


The World Health Organization (WHO) category "AML with recurrent genetic abnormalities" accounts for approximately 20-30% of AML cases[1]. The 2016 classification describes nine specific AML subtypes based on structural rearrangements or genetic mutations. There are also two provisional entities: AML with mutated RUNX1 and AML with BCR-ABL1.

Acute myeloid leukemia with balanced translocation/inversion

The recurrent genetic abnormalities in acute myeloid leukemia (AML) have an important role in predicting remission rate, relapse, treatment selection, and overall survival. The well-characterized balanced translocations/inversions include t(15;17)(q24.1;q21.2), t(8;21)(q22;q22.1), t(9;11)(p21.3;q23.3), and inv(16)(p13.1q22) or t(16;16)(p13.1;q22)[2]. Molecular studies have shown that these structural chromosome rearrangements create a fusion gene(s) encoding a chimeric protein. The altered expression and/or structure of cellular gene products leads to functional activation that may contribute to the initiation or progression of leukemogenesis[3]. Many other structural aberrations have been identified as recurrent in AML patients, but these entities are not as well characterized[4]. AML with t(8;21)(q22;q22.1), t(16;16)(p13.1;q22) or inv(16)(p13.1;q22), and acute promyelocytic leukemia with PML-RARA are considered to be acute leukemia without regard to blast cell count. It is controversial whether all cases with t(9;11)(p21.3;q23.3), t(6;9)(p23;q34.1), inv(3)(q21.3q26.2), t(3;3)(q21.3;q26.2), or t(1;22)(p13.3;q13.1) as well as AML with the BCR-ABL1 fusion should be categorized as AML when the blast cell count is <20%[1].

Acute myeloid leukemia with gene mutations

AML has long been associated with chromosomal rearrangements, but now it is understood that genetic mutations also play a prominent role in tumorigenesis. A landmark study published in 2013 by the Cancer Genome Atlas Research Network used the genetic data of 200 cases of de novo AML to identify 23 genes with a significantly high prevalence of mutations. The current WHO classification incorporates the previous provisional entities of AML with mutated nucleophosmin (NPM1) and AML with mutated CCAAT/enhancer binding protein alpha (CEBPA), with the clarification that the latter refers only to biallelic CEBPA mutations. It also introduces two new provisional entities: AML with mutated runt-related transcription factor 1 (RUNX1) and AML with a BCR, RhoGEF, and GTPase activating protein (BCR)-ABL proto-oncogene 1 (ABL1) gene fusion (BCR-ABL1)[5]. Since the publication of the WHO classification, additional novel recurrent gene mutations have been identified. DMNT3A, TET2, IDH1/2, ASXL1, and PTPN11 are among the genes most commonly mutated, some of which are considered initiating or “founder” mutations, whereas others are secondary events involved in disease progression[6]. In addition, a greater understanding of recurrent mutations in AML has led to the development of a number of targeted therapeutic drugs. Most notably, the identification of FLT3 internal tandem duplications (FLT3-ITD) and tyrosine kinase domain mutations (FLT3-TKD) has facilitated the FDA-approval of the tyrosine kinase inhibitor midostaurin in 2017[7]. More recently, a selective inhibitor of mutated IDH2, enasidenib, was approved for the treatment of relapsed or refractory IDH2-mutated AML[8].

WHO Classification Pages (Includes Links to Content)

Other Related Pages (Includes Links to Content)

Additional Information



  1. 1.0 1.1 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, Seibert R, Editors. IARC Press: Lyon, France, p130-145.
  2. Mrózek, Krzysztof; et al. (2009). "Molecular signatures in acute myeloid leukemia". Current Opinion in Hematology. 16 (2): 64–69. doi:10.1097/MOH.0b013e3283257b42. ISSN 1531-7048. PMC 4209289. PMID 19468266.
  3. Mitelman, Felix; et al. (2007). "The impact of translocations and gene fusions on cancer causation". Nature Reviews. Cancer. 7 (4): 233–245. doi:10.1038/nrc2091. ISSN 1474-175X. PMID 17361217.
  4. Walker, Alison; et al. (2013). "New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: cancer and leukemia group B 8461". Genes, Chromosomes & Cancer. 52 (4): 385–401. doi:10.1002/gcc.22036. ISSN 1098-2264. PMC 3874732. PMID 23225546.
  5. Song, Xiaolu; et al. (2018). "Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001-2013". Acta Haematologica. 139 (2): 115–127. doi:10.1159/000486228. ISSN 1421-9662. PMID 29455198.
  6. Lin, Pei; et al. (2015). "Acute Myeloid Leukemia With Recurrent Genetic Abnormalities Other Than Translocations". American Journal of Clinical Pathology. 144 (1): 19–28. doi:10.1309/AJCP97BJBEVZEUIN. ISSN 1943-7722. PMID 26071459.
  7. Stone, Richard M.; et al. (2017). "Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation". The New England Journal of Medicine. 377 (5): 454–464. doi:10.1056/NEJMoa1614359. ISSN 1533-4406. PMC 5754190. PMID 28644114.
  8. Stein, Eytan M. (2018). "Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia". Future Oncology (London, England). 14 (1): 23–40. doi:10.2217/fon-2017-0392. ISSN 1744-8301. PMID 29243965.


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