What is the role of genetics in the diagnosis and management of acute myeloid leukemia (AML)?

Updated: Dec 17, 2018
  • Author: Ari VanderWalde, MD, MPH, MA, FACP; Chief Editor: Karl S Roth, MD  more...
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The diagnosis, prognosis, and treatment of acute myeloid leukemia (AML) has been transformed over the past 15 years from a disease defined, classed, and staged based on histologic characteristics alone to a disease classified largely based on genetic, genomic, and molecular characteristics. Cytogenetic analysis of AML has become essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. [1, 2]

The risk pattern in AML is determined not only by cytogenetic abnormalities, such as chromosomal deletions, duplications, or substitutions, but also by the elucidation of certain molecular mutations leading to over- or under-expressions of one of many proteins.

Cytogenetic studies performed on bone marrow in patients with AML play a crucial role in characterizing the leukemia, helping determine disease aggressiveness, response to treatment, and prognosis. [3] For example, the finding of a translocation between chromosomes 15 and 17, or t(15;17), is associated with a diagnosis of acute promyelocytic leukemia (APL), a subtype of AML that is treated and monitored differently than other subtypes. [4]

The commonly used French American British (FAB) classification [5] as well as the more recent World Health Organization (WHO) classification [6] use a variety of factors to classify AML as poor-risk, intermediate-risk, and better-risk disease. In general, better-risk disease is associated with long-term survival of up to 65%, medium-risk disease is associated with long-term survival of about 25%, and poor-risk disease is associated with long-term survival of less than 10%.

Cytogenetic abnormalities associated with disease risk are shown in the Table. [7, 8]

Table. Cytogenetic Risk Factors (Open Table in a new window)

Risk Group

Cytogenetic Abnormality

Better Risk

inv(16), t(16;16), t(8;21), t(15;17)

Intermediate Risk

Normal cytogenetics, +8, t(9;11); other chromosomal abnormalities

Poor Risk

-5, 5q-, -7, 7q-, 11q23 other than t(9;11), inv(3), t(3;3), t(6;9),

t(9;22), complex findings (≥3 clonal chromosomal abnormalities)

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