Table 2.
Oncogenic potential of hematopoietic-related TFs.
| TF gene symbol | Functional domain | MGI Mouse BMF/HM phenotype | Embryonic lethality | Constraint | COSMIC no. of LOFs | Malignant fusions | Biallelic Variants Observed | Known CHIP genes | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Het mice | Hom mice | Human | LOEUF | pLI | Domain | Average constraint | Somatic | HM specific | |||||||
| Known BMF/HM TFs | RUNX1 | RUNT TAD |
Yes | No | Yes | NA/ Miscarriage observed |
0.44 | 0.65 | RUNT | 0.48, intolerant | 819 (23.9%) | AML1/MDS1, AML1/ETO, AML1/MDS1/EAI1, AML1/FOG2, RUNX1/YTHDF2, RUNX1/SH3D19, RUNX1/ZNF687 | AML1-ETO AML1-FOG2 AML-TEL |
Yes | Yes (rare) |
| CEBPA | TAD1 TAD2 DBD Zip |
Yes | No | Die ~4-10 h after birth | NA | 1.18 | 0.55 | Zip | 0.5032, intolerant | 711 (43.1%) | No somatic lesions found | No HM specific malignant fusions found | Yes | No | |
| GATA2 | TAL1 TAL2 ZF 1 ZF 2 |
Yes | No | Yes | NA/ Miscarriage observed |
0.29 | 0.98 | ZF 1 ZF 2 |
0.13, highly intolerant 0.149, highly intolerant |
63 (6.67%) | inv(3)(q21q26) | inv(3)(q21q26) | No (rare) | No | |
| PAX5 | OP, HD TA ID |
Yes | No | Yes | NA | 0.17 | 1 | Paired domain | 0.23, intolerant | 80 (4.3%) | No somatic lesions found | PAX5/NOL4L | Yes | No | |
| MECOM/EVI1 | ZF (x10) AD |
Yes | No | Yes | Yes | 0.14 | 1 | ZF, ZF, ZF |
0.24, intolerant 0.28, intolerant 0.08, highly intolerant |
115 (8.69%) | EVI1/RBPH1 | EVI1/GR6 | No | No | |
| STAT3 | NTD, CC, DBD, LD, SH2, TAD | Yes | No | Yes | NA/ Miscarriage observed |
0.10 | 1 | NTD, CC, DBD, LD, SH2, TAD | 0.19, intolerant | 56 (3.67%) | No somatic lesions found | No HM specific malignant fusions found | No | Yes | |
| GATA1 | AD ZF 1 ZF 2 |
Yes | No | Yes | Yes (Males)/ Miscarriage observed |
0.32 | 0.95 | ZF 1, ZF 2 |
0.18, intolerant 0.17, highly intolerant |
269 (34.1%) | No somatic lesions found | MYB-GATA1 | No | No | |
|
ETV6
(TEL) |
HLH ETS |
Yes | No | Yes | NA/ Miscarriage observed |
0.32 | 0.97 | ETS | 0.173, highly tolerant | 126 (7.3%) | ETV6/PDGFRB, ETV6/MDS2, ETV6/NTRK3, | ETV6/AML1, ETV6/JAK2, ETV6/RUNX1, ETV6/MN1, ETV6/ACS2, ETV6/ABL2, ETV6/ARNT, ETV6/BTL, ETV6/PER1 |
Yes | No | |
| FLI1 | ETS | Yes | No | No | NA | 0.28 | 0.99 | ETS | 0.0953, highly intolerant | 22 (1.97%) | FLI1/EWS | No HM specific malignant fusions found | Yes | No | |
| IKZF1 | ZF (x6) | Yes | No | Yes | NA | 0.16 | 1 | ZF | 0.1086, highly intolerant | 80 (3.41%) | No somatic lesions found | IKAROS/BCL6 | No | No | |
| IKZF3 | ZF (x6) | Yes | No | No | NA | 0.29 | 0.98 | ZF | 0.31, intolerant | 29 (2.80%) | No somatic lesions found | No HM specific malignant fusions found | No | No | |
| IKZF5 | ZF (x5) | Yes | No | No | NA | 0.46 | 0.78 | ZF | No data available | 32 (13.56%) | No somatic lesions found | No HM specific malignant fusions found | No | No | |
| Strong candidate BMF/HM TFs | GATA3 | TAL1 TAL2 ZF 1 ZF 2 |
Yes | No | Yes | Yes | 0.39 | 0.9 | ZF 1, ZF 2 |
0.12, highly intolerant, 0.31, intolerant |
784 (43.1%) | No somatic lesions found | No HM specific malignant fusions found | No | No |
|
SPI1
(PU.1) |
AD PEST ETS |
Yes | No | Yes | NA | 0.24 | 0.98 | ETS | 0.1261, highly intolerant | 6 (1.86%) | No somatic lesions found | No HM specific malignant fusions found | No | No | |
| ERG | PNT ETS |
Yes | No | Yes | NA | 0.33 | 0.96 | ETS | 0.2526, intolerant | 66 (3.42%) | ERG1, ERG2, ERG/TMPRSS2, ERG/EWS, ERG/FUS | ERG/FUS | No | No | |
Oncogenic potential of known BMF and/or HM predisposition TFs, as well as strong candidate BMF and/or HM predisposition TFs mapped using mouse phenotypes, constraint scores, variants observed and malignant fusions. Mouse phenotypes collated through Mouse MGI (25–27), and mousephenotype.org (28), constraint scoring (LOEUF, pLI and No. of LOF) extracted from gnomAD (29), domain constraint calculated from MetaDome (30), and somatic mutations obtained from COSMIC (31).
NA, not applicable.