How do genetics affect the prognosis 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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Answer

Answer

In addition to cytogenetic abnormalities, several molecular abnormalities have been shown to have prognostic importance in patients with AML.

FLT3 is the most commonly mutated gene in AML and appears to be activated in one third of AML cases. Internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3 are seen in 25% of AML cases, while others show mutations in the activation loop of FLT3. Patients with FLT3 -ITD tend to have a poor prognosis, and in a patient with normal cytogenetics (otherwise intermediate risk), the presence of FLT3 -ITD mutation changes the patient to poor risk. [8, 10, 11, 12, 13, 14, 15]

Mutation in NPM1 is generally favorable; patients with this mutation show increased response to chemotherapy and improved survival (changes otherwise intermediate-risk patients into better-risk). However, if present together with the FLT3 mutation, this survival benefit is negated. [16] Mutations in CEBPA are detected in 15% of patients with normal cytogenetics and are associated with a longer remission duration and longer overall survival. [17] Of note, the presence of c-KIT mutations in patients with otherwise favorable cytogenetic markers (eg, t(8:21), inv(16)) confers a higher risk of relapse and would place an otherwise better-risk patient into the intermediate-risk category. [8, 18]

Other molecular markers, such as IDH1, IDH2, and DNMT3A, have been suggested to be predictive of risk and response to treatment. However, the relationship between these markers and risk of relapse/death has not been fully elucidated, and tests for these markers are not routinely available. As such, they are not typically included in genetic/molecular risk classification schema. [8]


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