Table 2 Functional categories of genes that are commonly mutated in acute myeloid leukemia (AML)
Functional category | Gene members | Role in AML Leukemogenesis |
|---|---|---|
Myeloid transcription-factor genes | Transcription factor fusions by chromosomal rearrangements, such as t(8;21)(q22;q22); RUNX1-RUNX1T1 and inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 GATA2, RUNX1 and CEBPA | Transcriptional deregulation and impaired hematopoietic differentiation. |
Nucleophosmin (NPM1) gene | NPM1 | Aberrant cytoplasmic localization of NPM1 and its interacting proteins |
Tumor suppressor genes | TP53, WT1, PHF6 | Transcriptional deregulation and impaired degradation via the negative regulator (MDM2 and PTEN oncogenes) |
Signaling genes | FLT3, KIT, PTPN11, RAS | Proliferative advantage through the RAS-RAF, JAK-STAT, and PI3K-AKT signaling pathways |
DNA methylation | DNMT3A, TET2, IDH1, IDH2 | Deregulation of DNA methylation and oncometabolite production |
Chromatin modifier | ASXL1, EZH2 and KMT2A | Deregulation of chromatin modification and impairment of methyltransferases function |
Cohesin complex | STAG1, STAG2, RAD21, SMC1A, SMC3, | Impairment of accurate chromosome segregation and transcriptional regulation |
Splicing factors | SRSF2, SF3B1, U2AF1, ZRSR2 | Deregulated RNA processing and aberrant splicing patterns |