Table 1.

Gene mutation frequency and clinical implications

Gene name	Function of native genes/proteins	Mutant frequency in AML	Mutant gene clinical significance
FLT3	FLT3 gene located on chromosome 13 A receptor tyrosine kinase Exclusively in hematopoietic compartment Mediates HSC survival, proliferation and differentiation	FLT3 mutation ~ 30% of all AML FLT3-ITD ~ 25% of AML FLT3-TKD ~ 7–10% of AML	Associated with R/R AML and poor OS Favorable prognosis co-mutation NPM1 with FLT3-TKD ELN guidelines recommend upfront testing for FLT3 and AR Recommend to use targeted FLT3 inhibitors to improve outcomes
NPM1	NPM1 gene located on chromosome 5 Multifunctional phosphoprotein in the granular portion of nucleolus Regulates multiple cellular events Regulates key tumor suppressor proteins ARF, p53 and MDM2	~ 30% of all AML 40–60% with normal karyotypes	Favorable mutant Higher CR rate Improved OS Lower cumulative incidence of relapse A stable marker for assessment of MRD
CEBPA	CEBPA gene located on chromosome 19 A transcription factor Strongly implicated in myelopoiesis Control proliferation and differentiation of myeloid progenitors	10–20% of AML with normal karyotypes ~ 50% with biCEBPA	WHO recognizes biCEBPA as a unique entity Favorable prognosis of biCEBPA mutations with standard therapy biCEBPA more likely co-mutate with TET2 and GATA2 moCEBPA more likely co-mutate with NPM1, FLT-3 ITD/TKD, and IDH2
RUNX1	RUNX1 gene located on chromosome 21 Regulate critical processes in hematopoiesis Define definitive hematopoietic stem cell	~ 10–15% of all AML	Involved in t(8;21) in AML Fusion protein between RUNX1 and ETO A new entity “AML with mutated RUNX1” Associated with inferior outcome Co-mutation DNMT3A and RUNX1 with inferior OS in age < 60 AML
ASXL1	ASXL1 gene located on chromosome 20q11 An epigenetic modulator Mutant ASXL1 protein distracts hematopoiesis and promotes myeloid transformation by altering histone modifications	~ 15–20% of all AML 5 times more common in older patients (≥ 60 years) than younger patients (< 60 years)	Associated with inferior OS More coexist with RUNX1, IDH2 Clonal marker for R/R AML
TP53	TP53 genes located on chromosome 17p Critical role in tumor suppression Mutation/deletion causes different tumors	< 10% of de novo AML 20–37% of patients with sAML/tAML ~ 70% of patients with a complex karyotype Prevalent with R/R AML	Poor OS with standard therapy More frequent in older patients More frequent with 17p mutations More frequent with aberrations in chromosomes 5 and 7 More likely in R/R AML