Identifying prognostic gene panels in acute myeloid leukemia

Expert Rev Hematol. 2023 Apr;16(4):277-287. doi: 10.1080/17474086.2023.2193322. Epub 2023 Mar 29.

Abstract

Introduction: Acute myeloid leukemia (AML) is a heterogeneous disease currently including 12 entities defined by genetic findings with remarkable differences in prognosis and targeted therapies availability. Therefore, identification of genetic abnormalities by efficient techniques has become a necessary tool in routine clinical practice for AML patients.

Areas covered: In the present review, we will focus on our current knowledge of relevant prognosis gene mutations in AML, as recently updated by European Leukemia Net Leukemia risk classification.

Expert opinion: About 25% of newly diagnosed younger AML patients will be promptly classified as favorable prognosis by demonstrating the presence of NPM1 mutations or CBF rearrangements by qRTPCR, allowing for implementing molecular measurable residual disease-guided chemotherapy-based protocols. In fit AML patients, rapid detection of FLT3ITD is mandatory to associate midostaurin or quizartinib to treatment and assignment to intermediate prognosis. Conventional cytogenetics and FISH still have a role for detection adverse prognosis karyotypes and KMT2A, MECOM, or NUP98 gene rearrangements. Further genetic characterization is performed with NGS panels including favorable prognosis gene CEBPA bZIP and adverse prognosis genes, such as TP53 and myelodysplasia associated genes.

Keywords: AML; FLT3; NPM1; TP53; prognosis; splicesosome; targeted therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Nucleophosmin*
  • Prognosis
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Nucleophosmin
  • fms-Like Tyrosine Kinase 3