Several recurrent somatic mutations have been identified as important features in defining the molecular landscape of AML. Targeting mutations such as FLT3 remained an area with active investigations and variable success while targeting other common mutations such as NPM1, DNMT3A, and TET2 remains challenging.

Cytogenetic characterization of AML: These abnormalities include: AML with t(8;21)(q22;q22); RUNX1-RUNX1T1, AML with inv (16)(p13.1q22) or t (1 6; 1 6) (p 1 3. 1; q 2 2); C B F B - M Y H 1 1, A M L w i t h t(15;17)(q22;q12); PML-RARA, AML with t(9;11)(p22;q23);MLLT3-MLL, AML with t(6;9)(p23;q34); DEK-NUP214, AML with inv (3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1, AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL14, A recent revision of WHO classification in 2016 has recognized new provisional category of AML with BCR-ABL1. Patients with BCR-ABL1 AML are less likely to have splenomegaly or peripheral basophilia and usually have lower bone marrow cellularity and myeloid/erythroid ratios compared to CML-BC.

Mutations in signaling pathways: Mutations in FLT3 receptor can lead to constitutive activation that in turn can lead to decrease in apoptosis and increase in leukemia proliferation and survival. Patients with FLT3/ITD mutations typically have high white cell counts at disease presentation and have normal or intermediate risk karyotypes. FLT3/TKD mutations tend to confer slightly better prognosis. NPM1 mutations usually occur in exon 12 in the C-terminus of the protein and can lead to cytoplasmic localization of NPM1 protein. Studies have shown that NPM1 mutations usually carry a favorable prognosis in the absence of FLT3-ITD and mainly in the presence of IDH1-2.

Other gene mutations in AML: ASXL1 gene encodes a chromatin binding protein, which in turn enhance or repress gene transcription in localized areas by chromatin structure modification. The overall frequency of ASXL1 mutations in AML is approximately 3–5% but its incidence is higher in patients with intermediate risk AML. DNMT3A is a DNA methyltransferase that regulates epigenetic alterations through DNA methylation. DNMT3A mutations are frequently found with FLT3-ITD, NPM1, IDH1-2 mutations though rarely associated with t (15; 17) and CBF leukemia's. IDH1 and IDH2 are two enzymes that play an important role in DNA methylation and histone modification and affect the active isocitrate binding site and lead to increased level of 2-hydroxyglutarate. IDH2 mutations occur in 8–12% of adult AML. 2-HG can be detected in vast excess in the serum and BM of AML patients with IDH1/2 mutations, suggesting that it may serve as a biomarker for this genetically defined subset of AML patients and as a measure of residual disease after AML therapy.

Mutations in cohesion complex members; BCOR, PHF6;

Mutations in splicing machinery: The most common splicing factor gene abnormalities involved in AML are SF3B1, U2AF1, SRSF2, and ZRSR2. These mutations are mutually exclusive and can be defined as founder mutations or associated with certain phenotype in a subset of patients such as SF3B1 mutations in MDS patients with ring sideroblasts and SRSF2 in chronic CMML.