Prevalence, association, and prognosis of mutations detected in AML presenting in younger adults (16-60 y)
| Category/mutant gene . | % . | Associated mutations/ chromosomal abnormalities . | Prognostic implications . |
|---|---|---|---|
| DNA methylation | |||
| DNMT3A | 20 | NPM1, FLT3-ITD, NK | Adverse |
| DNA demethylation | |||
| TET2 | 8 | ASXL1, NK | Poorer in IR-AML |
| IDH1 | 7 | NPM1, NK | Poorer in FLT3-ITD-neg AML |
| IDH2-R140 | 7 | NPM1, NK | Favorable |
| IDH2-R172 | 2 | NK | Adverse |
| WT1 | 9 | FLT3-ITD | Poorer in NK-AML |
| Activated signaling | |||
| FLT3-ITD | 27 | NPM1, DNMT3A, NK, t(15;17)/ PML-RARA, t(6;9)/DEK-NUP214, t(5;11)/NUP98-NSD1 | Poorer in IR-AML |
| FLT3-TKD | 7 | inv(16)/CBFB-MYH11, | Variable according to study |
| t(15;17)/PML-RARA | |||
| NRAS | 11 | inv(16)/CBFB-MYH11, | NS |
| t(3;5)/NPM1-MLF1, 11q23/MLL-X | |||
| KRAS | 5 | inv(16)/CBFB-MYH11, 11q23/MLL-X | NS |
| PTPN11 | 5 | NPM1 | ND |
| NF1* | 4 | MK, −17/17q | ND |
| KIT | 4 | t(8;21)/RUNX1/RUNX1T1, inv(16)/CBFB-MYH11 | Poorer outcome in CBF AML |
| CBL | 1 | TBC | |
| Myeloid transcription factors | |||
| RUNX1 | 5 | MLL-PTD, ASXL1, IDH2, NK, +13 | Adverse |
| biCEBPA | 4 | GATA2, NK | Favorable |
| Tumor suppressor/ multifactorial | |||
| TP53* | 8 | Complex, MK, −5/-5q, −7/-7q, −17/17p | Adverse |
| NPM1 | 33 | DNMT3A, IDH1, IDH2-R140, | Favorable in absence of FLT3-ITD and mutant DNMT3A |
| FLT3-ITD, PTPN11, cohesin, NK | |||
| Chromatin regulation | |||
| ASXL1 | 5 | RUNX1, IDH2-R140, | Poorer in IR-AML |
| t(8;21)/RUNX1-RUNX1T1, +8 | |||
| MLL-PTD | 5 | +11, NK, RUNX1, FLT3 | Adverse |
| PHF6 | 3 | RUNX1 | TBC |
| ASXL2 | 2 | t(8;21)/RUNX1-RUNX1T1 | ND |
| BCOR | 1 | NK, DNMT3A | TBC |
| EZH2 | 1 | ND | |
| Spliceosome | |||
| SRSF2 | 2 | +13, ASXL1, RUNX1, IDH1/2 | ND |
| SF3B1 | 3 | RUNX1, inv(3)/GATA2-EVI1 | |
| U2AF1 | 2 | ||
| ZRSR2 | <1 | ||
| Cohesin | |||
| RAD21 | 6-9 | NPM1 | NS |
| SMC1A | |||
| SMC3 | |||
| STAG1 | |||
| STAG2 |
| Category/mutant gene . | % . | Associated mutations/ chromosomal abnormalities . | Prognostic implications . |
|---|---|---|---|
| DNA methylation | |||
| DNMT3A | 20 | NPM1, FLT3-ITD, NK | Adverse |
| DNA demethylation | |||
| TET2 | 8 | ASXL1, NK | Poorer in IR-AML |
| IDH1 | 7 | NPM1, NK | Poorer in FLT3-ITD-neg AML |
| IDH2-R140 | 7 | NPM1, NK | Favorable |
| IDH2-R172 | 2 | NK | Adverse |
| WT1 | 9 | FLT3-ITD | Poorer in NK-AML |
| Activated signaling | |||
| FLT3-ITD | 27 | NPM1, DNMT3A, NK, t(15;17)/ PML-RARA, t(6;9)/DEK-NUP214, t(5;11)/NUP98-NSD1 | Poorer in IR-AML |
| FLT3-TKD | 7 | inv(16)/CBFB-MYH11, | Variable according to study |
| t(15;17)/PML-RARA | |||
| NRAS | 11 | inv(16)/CBFB-MYH11, | NS |
| t(3;5)/NPM1-MLF1, 11q23/MLL-X | |||
| KRAS | 5 | inv(16)/CBFB-MYH11, 11q23/MLL-X | NS |
| PTPN11 | 5 | NPM1 | ND |
| NF1* | 4 | MK, −17/17q | ND |
| KIT | 4 | t(8;21)/RUNX1/RUNX1T1, inv(16)/CBFB-MYH11 | Poorer outcome in CBF AML |
| CBL | 1 | TBC | |
| Myeloid transcription factors | |||
| RUNX1 | 5 | MLL-PTD, ASXL1, IDH2, NK, +13 | Adverse |
| biCEBPA | 4 | GATA2, NK | Favorable |
| Tumor suppressor/ multifactorial | |||
| TP53* | 8 | Complex, MK, −5/-5q, −7/-7q, −17/17p | Adverse |
| NPM1 | 33 | DNMT3A, IDH1, IDH2-R140, | Favorable in absence of FLT3-ITD and mutant DNMT3A |
| FLT3-ITD, PTPN11, cohesin, NK | |||
| Chromatin regulation | |||
| ASXL1 | 5 | RUNX1, IDH2-R140, | Poorer in IR-AML |
| t(8;21)/RUNX1-RUNX1T1, +8 | |||
| MLL-PTD | 5 | +11, NK, RUNX1, FLT3 | Adverse |
| PHF6 | 3 | RUNX1 | TBC |
| ASXL2 | 2 | t(8;21)/RUNX1-RUNX1T1 | ND |
| BCOR | 1 | NK, DNMT3A | TBC |
| EZH2 | 1 | ND | |
| Spliceosome | |||
| SRSF2 | 2 | +13, ASXL1, RUNX1, IDH1/2 | ND |
| SF3B1 | 3 | RUNX1, inv(3)/GATA2-EVI1 | |
| U2AF1 | 2 | ||
| ZRSR2 | <1 | ||
| Cohesin | |||
| RAD21 | 6-9 | NPM1 | NS |
| SMC1A | |||
| SMC3 | |||
| STAG1 | |||
| STAG2 |
Mutations within the same functional category are negatively associated, and positive associations are listed.
bi, biallelic; IR, intermediate risk; ITD, internal tandem duplication; MK, monosomal karyotype; ND, not determined; NK, normal karyotype; NS, not significant; PTD, partial tandem duplication; TBC, to be confirmed; TKD, tyrosine kinase domain.
Includes mutations and gene deletions.