Mutational and cytogenetic features of 464 patients with WHO-defined MF, stratified by presence or absence of RAS/CBLMT
| Variable . | All patients (N = 464) . | RAS/CBLWT (n = 405; 89%) . | RAS/CBLMT (n = 59; 11%) . | P (RAS/CBLWT vs RAS/CBLMT) . |
|---|---|---|---|---|
| MPN drivers, n (%) | ||||
| JAK2M | 289 (62) | 258 (64) | 31 (53) | .09 |
| CALRM | 115 (25) | 101 (25) | 14 (24) | .90 |
| MPLM | 32 (7) | 28 (7) | 4 (7) | .99 |
| Triple negative | 41 (9) | 30 (7) | 11 (19) | .0045 |
| Epigenetic regulators of methylation, n (%) | ||||
| DNMT3AM | 25 (5) | 23 (6) | 2 (3) | .47 |
| IDH1/2M | 15 (3) | 11 (3) | 4 (7) | .10 |
| TET2M | 91 (20) | 79 (20) | 12 (20) | .88 |
| Chromatin regulating genes, n (%) | ||||
| ASXL1M | 153 (33) | 111 (27) | 42 (71) | <.0001 |
| EZH2M [463] | 41 (9) | 29 (7) | 12 (20) | .0009 |
| Pre-mRNA splicing mutations, n (%) | ||||
| SF3B1M [461] | 30 (7) | 24 (6) | 6 (11) | .17 |
| SRSF2M | 35 (8) | 23 (6) | 12 (20) | <.0001 |
| U2AF1M [461] | 25 (5) | 20 (5) | 5 (9) | .22 |
| ZRSR2M [318] | 26 (8) | 21 (7) | 5 (14) | .21 |
| Transcription factors and nucleosome assembly, n (%) | ||||
| NF-E2M [445] | 24 (5) | 24 (6) | 0 (0) | .07 |
| RUNX1M [461] | 15 (3) | 12 (3) | 3 (5) | .34 |
| SETBP1M [318] | 7 (2) | 4 (1) | 3 (8) | .0092 |
| Cell signaling, n (%) | ||||
| CSF3RM [318] | 8 (3) | 8 (3) | 0 (0) | .30 |
| KITM [460] | 4 (1) | 3 (1) | 1 (2) | .43 |
| SH2B3/LNKM [458] | 19 (4) | 15 (4) | 4 (7) | .23 |
| DNA damage response, n (%) | ||||
| TP53M, n (%) [462] | 22 (5) | 20 (5) | 2 (4) | .64 |
| HMRMT, n (%)* | ||||
| HMRMT [463] | 178 (38) | 134 (33) | 44 (75) | <.0001 |
| ≥2 HMRMTs [463]† | 62 (13) | 37 (9) | 25 (42) | <.0001 |
| Cytogenetics, n (%)‡ | ||||
| Abnormal karyotype [334] | 112 (34) | 96 (33) | 16 (36) | .67 |
| Favorable karyotype | 281 (84) | 248 (85) | 33 (75) | Reference |
| Unfavorable karyotype | 31 (9) | 25 (9) | 6 (14) | .22 |
| Very high-risk karyotype | 22 (7) | 17 (6) | 5 (11) | .13 |
| Variable . | All patients (N = 464) . | RAS/CBLWT (n = 405; 89%) . | RAS/CBLMT (n = 59; 11%) . | P (RAS/CBLWT vs RAS/CBLMT) . |
|---|---|---|---|---|
| MPN drivers, n (%) | ||||
| JAK2M | 289 (62) | 258 (64) | 31 (53) | .09 |
| CALRM | 115 (25) | 101 (25) | 14 (24) | .90 |
| MPLM | 32 (7) | 28 (7) | 4 (7) | .99 |
| Triple negative | 41 (9) | 30 (7) | 11 (19) | .0045 |
| Epigenetic regulators of methylation, n (%) | ||||
| DNMT3AM | 25 (5) | 23 (6) | 2 (3) | .47 |
| IDH1/2M | 15 (3) | 11 (3) | 4 (7) | .10 |
| TET2M | 91 (20) | 79 (20) | 12 (20) | .88 |
| Chromatin regulating genes, n (%) | ||||
| ASXL1M | 153 (33) | 111 (27) | 42 (71) | <.0001 |
| EZH2M [463] | 41 (9) | 29 (7) | 12 (20) | .0009 |
| Pre-mRNA splicing mutations, n (%) | ||||
| SF3B1M [461] | 30 (7) | 24 (6) | 6 (11) | .17 |
| SRSF2M | 35 (8) | 23 (6) | 12 (20) | <.0001 |
| U2AF1M [461] | 25 (5) | 20 (5) | 5 (9) | .22 |
| ZRSR2M [318] | 26 (8) | 21 (7) | 5 (14) | .21 |
| Transcription factors and nucleosome assembly, n (%) | ||||
| NF-E2M [445] | 24 (5) | 24 (6) | 0 (0) | .07 |
| RUNX1M [461] | 15 (3) | 12 (3) | 3 (5) | .34 |
| SETBP1M [318] | 7 (2) | 4 (1) | 3 (8) | .0092 |
| Cell signaling, n (%) | ||||
| CSF3RM [318] | 8 (3) | 8 (3) | 0 (0) | .30 |
| KITM [460] | 4 (1) | 3 (1) | 1 (2) | .43 |
| SH2B3/LNKM [458] | 19 (4) | 15 (4) | 4 (7) | .23 |
| DNA damage response, n (%) | ||||
| TP53M, n (%) [462] | 22 (5) | 20 (5) | 2 (4) | .64 |
| HMRMT, n (%)* | ||||
| HMRMT [463] | 178 (38) | 134 (33) | 44 (75) | <.0001 |
| ≥2 HMRMTs [463]† | 62 (13) | 37 (9) | 25 (42) | <.0001 |
| Cytogenetics, n (%)‡ | ||||
| Abnormal karyotype [334] | 112 (34) | 96 (33) | 16 (36) | .67 |
| Favorable karyotype | 281 (84) | 248 (85) | 33 (75) | Reference |
| Unfavorable karyotype | 31 (9) | 25 (9) | 6 (14) | .22 |
| Very high-risk karyotype | 22 (7) | 17 (6) | 5 (11) | .13 |
Bold P values indicate statistically significant results. Numbers in brackets are the number of patients with evaluable data.
The HMR category is defined as the presence of a mutation in any of the following genes: ASXL1, EZH2, SRSF2, and IDH1/2.
≥2 HMRMTs indicates the presence of 2 or more mutations in the ASXL1, EZH2, SRSF2, and IDH1/2 genes (2 or more mutations in the same gene are counted as 1).
According to the revised cytogenetic risk stratification.24