Acute Myeloid Leukemia with Myelodysplasia-Related Gene Mutations

Background/Objectives: Acute myeloid leukemia (AML) with myelodysplasia-related gene mutations (AML-MR), often referred to as secondary AML (s-AML) or AML-MRC, is an aggressive form of leukemia that typically arises from an antecedent myelodysplastic syndrome (MDS) but may also originate de novo. It is characterized by mutations in key genes associated with MDS that include some epigenetic regulators (ASXL1 and EZH2), splicing factors (SF3B1, SRSF2, U2AF1, and ZRSR2), and transcription factors (BCOR, RUNX1, and STAG2). The main objective of this review paper consists of analyzing recent studies that have improved the criteria for the characterization, definition, and classification of AML-MR. Methods: An extensive search of the most recent literature on the topic was performed, selecting and critically analyzing the most relevant studies. Results. The studies carried out in the last few years have provided an extensive molecular characterization of AML-MR, supporting sounder criteria for identification and a better definition with respect to other AML subtypes, particularly with respect to TP53-mutant AML. Conclusions: A unifying classification of AML-MR is now possible, allowing its identification as a unique, well-defined, and separate entity.