WHO 2022 / ICC 2022 AML

A major update in the 2022 framework is the lowering of the blast threshold from 20% to 10% for specific genetic drivers (e.g., KMT2A, DEK::NUP214, GATA2::MECOM). This acknowledges that these "MDS/AML" borderline cases behave biologically like AML and should be treated as such.

NPM1-mutated AML is now considered a distinct entity and is generally associated with a favorable prognosis, especially in the absence of FLT3-ITD. CEBPA mutations must specifically involve the basic leucine zipper (bZIP) region to be considered a defining favorable entity in the 2022 criteria.

The 2022 system refined the "Myelodysplasia-related" category, requiring specific cytogenetic features (e.g., complex karyotype, del[5q], -7) or mutations in a defined set of genes (e.g., ASXL1, BCOR, SF3B1) rather than just a prior history of MDS.