Genetic targets in mouse models with myelodysplasia and their implication in human MDS or MDS/MPN
| Gene symbol . | Frequency (%)* . | Predominant genetic aberration . | Reference . | |
|---|---|---|---|---|
| MDS . | MDS/MPN . | |||
| ASXL1 | 11-20.7 | 33-49† | Mutation | 68,,,,,-74 |
| BAP1 | 3‡ | Truncating mutation | 52 | |
| CD74-NID67 | + | Deleted in 5q- syndrome§ | ||
| CREBBP | + | 2 cases | Translocation¶ | 75,-77 |
| <2 | Mutation | 6 | ||
| CCNE1 (CYCLIN E) | ||||
| DICER | ||||
| DNMT3A | 0-13.5 | 0-6.8 | Mutation | 78 |
| EVI1 | + | Translocation | 79 | |
| 26-29 | Overexpressed in blood cells from MDS patients | 80,81 | ||
| MAP3K7 (TAK1) | 22† | Gene deletion | 55 | |
| miR145/146a | + | Significantly reduced expression in blood cells from patients with 5q- syndrome | 56 | |
| NPM1 | 0-5.8 | 0-14.3 | Mutation | 70,74,82,,,-86 |
| NRAS | 5.7-6.3 | 17-19 | G12D mutation# | 87,-89 |
| NUP98-HOXD13 | 1 case | Translocation | 90 | |
| POLG | ||||
| RUNX1 | 12-13.8 | 37† | D171N, S291fs# | 87,91 |
| SALL4b | ||||
| S100A9 | + | Increased number of myeloid cells expressing S100A9 are found in MDS patients | 64 | |
| TRAF6 | + | Possibly increased in blood cells of patients with 5q- syndrome | 92 | |
| Gene symbol . | Frequency (%)* . | Predominant genetic aberration . | Reference . | |
|---|---|---|---|---|
| MDS . | MDS/MPN . | |||
| ASXL1 | 11-20.7 | 33-49† | Mutation | 68,,,,,-74 |
| BAP1 | 3‡ | Truncating mutation | 52 | |
| CD74-NID67 | + | Deleted in 5q- syndrome§ | ||
| CREBBP | + | 2 cases | Translocation¶ | 75,-77 |
| <2 | Mutation | 6 | ||
| CCNE1 (CYCLIN E) | ||||
| DICER | ||||
| DNMT3A | 0-13.5 | 0-6.8 | Mutation | 78 |
| EVI1 | + | Translocation | 79 | |
| 26-29 | Overexpressed in blood cells from MDS patients | 80,81 | ||
| MAP3K7 (TAK1) | 22† | Gene deletion | 55 | |
| miR145/146a | + | Significantly reduced expression in blood cells from patients with 5q- syndrome | 56 | |
| NPM1 | 0-5.8 | 0-14.3 | Mutation | 70,74,82,,,-86 |
| NRAS | 5.7-6.3 | 17-19 | G12D mutation# | 87,-89 |
| NUP98-HOXD13 | 1 case | Translocation | 90 | |
| POLG | ||||
| RUNX1 | 12-13.8 | 37† | D171N, S291fs# | 87,91 |
| SALL4b | ||||
| S100A9 | + | Increased number of myeloid cells expressing S100A9 are found in MDS patients | 64 | |
| TRAF6 | + | Possibly increased in blood cells of patients with 5q- syndrome | 92 | |
Presented are the frequencies of sequence abnormalities observed in human MDS or MDS/ MPN patients. A + indicates that a perturbation was found but no frequency was reported.
In patients with chronic myelomonocytic leukemia.
One of 32 patients tested showed a mutation in BAP1.
Five percent to 10% of MDS patients show deletion of 5q.93,94 The region deleted in the mouse model represents the smallest commonly deleted region in an analysis of 16 5q- MDS patients.95
Crebbp translocations mostly involve therapy-related hematopoietic malignancies.
Other mutations in NRAS and Runx1 have been described as well in MDS patients.87,96