Clinical and laboratory features and subsequent events in SF3B1MT CMML, SF3B1WT CMML, and SF3B1MT MDS-RS patients
| Variable . | CMML with SF3B1MT (n = 40) . | CMML without SF3B1MT (n = 819) . | P (CMML with vs without SF3B1MT) . | SF3B1MT MDS-RS (n = 83) . | P (CMML with SF3B1MT vs SF3B1MT MDS-RS . |
|---|---|---|---|---|---|
| Median age (range), y | 74.5 (43-95) | 71.0 (2-95) | .07 | 74 (42-94) | .98 |
| Male sex | 26 (61.9) | 556 (67.9) | .44 | 53 (63.9) | 1.00 |
| Median hemoglobin (range), g/dL | 9.4 (6.8-13.5) | 10.9 (1.4-16.9) | .01 | 9.5 (7-13.5) | 1.00 |
| Median WBC (range), × 109/L | 8.0 (2.5-96.1) | 13.3 (1.3-288.6) | .009 | 5 (1.5-13.1) | .007 |
| Median ANC (range), × 109/L | 3.3 (0.4-54.7) | 6.5 (0.0-155.6) | .009 | 2.7 (0.4-9.4) | .14 |
| Median AMC (range), × 109/L | 1.6 (1.2-11.5) | 2.7 (1-84.0) | .007 | 0.4 (0-1.0) | .005 |
| Median platelets (range), × 109/L | 138.0 (12-840) | 98.0 (2-1945) | .006 | 259.0 (13-599) | .03 |
| Presence of IMCs | 16 (41.0) | 478 (60.4) | .06 | NA | .005 |
| Median PB blast (range), % | 0 (0-3) | 0 (0-19) | .07 | 0 (0-0) | .009 |
| Median BM blast (range), % | 3 (0-16) | 3 (0-19) | .9 | 1 (0-4) | .004 |
| Presence of RSs* | 15/17 (88) | 68/482 (14) | <.001 | 83 (100) | 1.00 |
| Median VAF SF3B1 (range), % | 40.5 (8-48) | NA | NA | 41 (9-49) | 1.00 |
| Total no. of evaluable patients with FAB CMML subtypes | 40 | 817 | .04 | NA | NA |
| dCMML | 30 (75) | 399 (48.8) | NA | ||
| pCMML | 10 (25) | 418 (51.2) | NA | ||
| Total no. of evaluable patients with WHO 2016 CMML subtypes | 39 | 778 | .25 | NA | NA |
| CMML-0 | 29 (74.4) | 461 (59.3) | NA | ||
| CMML-1 | 7 (17.9) | 184 (23.7) | NA | ||
| CMML-2 | 3 (7.7) | 133 (17.1) | NA | ||
| Total no. of evaluable patients with CPSS-Mol cytogenetic risk stratification | 39 | 752 | .03 | 83 | 1.00 |
| Low | 29 (74.4) | 555 (73.8) | 66 (79.5) | ||
| Intermediate | 9 (23.1) | 85 (11.3) | 13 (15.7) | ||
| High | 1 (2.6) | 112 (14.9) | 4 (4.8) | ||
| Total no. of evaluable patients with NGS analysis | 40 | 567 | 83 | ||
| Epigenetic regulators | |||||
| TET2 | 17 (42.5) | 295 (52.0) | .39 | 21 (25.6) | .15 |
| IDH1 | 2 (5.0) | 5 (0.9) | .14 | 0 (0) | .23 |
| IDH2 | 2 (5.0) | 29 (5.1) | 1.00 | 1 (1.2) | .50 |
| DNMT3A | 7 (17.5) | 34 (6.0) | .05 | 16 (19.3) | 1.00 |
| Chromatin regulators | |||||
| ASXL1 | 4 (10.0) | 277 (48.9) | .03 | 11 (13.3) | 1.00 |
| EZH2 | 1 (2.5) | 45 (7.9) | .50 | 2 (2.4) | 1.00 |
| Transcription factor | |||||
| RUNX1 | 8 (20.0) | 78 (13.8) | .41 | 2 (2.4) | .007 |
| Spliceosome component genes | |||||
| SRSF2 | 5 (12.5) | 253 (44.6) | .02 | 2 (2.4) | .09 |
| U2AF1 | 0 (0) | 42 (7.4) | .18 | 0 (0) | 1.00 |
| ZRSR2 | 1 (2.5) | 36 (6.3) | .66 | NA | NA |
| Cell signaling | |||||
| NRAS | 5 (12.5) | 90 (15.9) | .72 | NA | NA |
| KRAS | 0/17 (0) | 19/313 (6.1) | .75 | NA | NA |
| CBL | 3 (7.5) | 88 (15.5) | .28 | 2 (2.4) | .62 |
| PTPN11 | 0/17 (0) | 9/313 (2.9) | .66 | NA | NA |
| JAK2 | 7 (17.5) | 40 (7.1) | .03 | 1 (1.2) | .01 |
| CSF3R | 0/17 (0) | 4/313 (1.3) | .76 | 3 (3.6) | 1.00 |
| KIT | 1 (2.5) | 24 (4.2) | .90 | NA | NA |
| MPL | 0 (0) | 5 (0.9) | .92 | NA | NA |
| CALR | 0/17 (0) | 1/313 (0.3) | .92 | NA | NA |
| Tumor suppressor gene | |||||
| TP53 | 1 (2.5) | 16 (2.8) | 1.00 | 3 (3.6) | 1.00 |
| Other | |||||
| SETBP1 | 0 (0) | 62 (10.9) | .10 | 2 (2.4) | 1.00 |
| No. of assessable patients for stratification by the Mayo Molecular Model | 40 | 809 | .02 | NA | NA |
| Low risk | 6 (15.0) | 93 (11.5) | NA | ||
| Intermediate-1 risk | 20 (50.0) | 265 (32.8) | NA | ||
| Intermediate-2 risk | 12 (30.0) | 237 (29.3) | NA | ||
| High risk | 2 (5.0) | 214 (26.5) | NA | ||
| No. of assessable patients for stratification by the GFM Model | 40 | 809 | .04 | NA | NA |
| Low risk | 27 (67.5) | 358 (44.3) | NA | ||
| Intermediate risk | 11 (27.5) | 320 (39.6) | NA | ||
| High risk | 2 (5.0) | 131 (16.2) | NA | ||
| No. of assessable patients for stratification by the IPSS-R | 40 | 748 | .14 | 83 | .43 |
| Very low | 7 (17.5) | 171 (22.9) | 26 (31.3) | ||
| Low | 23 (57.5) | 274 (36.6) | 46 (55.4) | ||
| Intermediate | 5 (12.5) | 174 (23.3) | 7 (8.4) | ||
| High | 5 (12.5) | 88 (11.8) | 4 (4.8) | ||
| Very high | 0 (0.0) | 41 (5.5) | 0 (0.0) | ||
| Deaths | 18 (45.0) | 461 (56.2) | — | 56 (67.5) | — |
| Leukemic transformation | 6 (15.0) | 159 (19.4) | — | 2 (2.4) | — |
| Variable . | CMML with SF3B1MT (n = 40) . | CMML without SF3B1MT (n = 819) . | P (CMML with vs without SF3B1MT) . | SF3B1MT MDS-RS (n = 83) . | P (CMML with SF3B1MT vs SF3B1MT MDS-RS . |
|---|---|---|---|---|---|
| Median age (range), y | 74.5 (43-95) | 71.0 (2-95) | .07 | 74 (42-94) | .98 |
| Male sex | 26 (61.9) | 556 (67.9) | .44 | 53 (63.9) | 1.00 |
| Median hemoglobin (range), g/dL | 9.4 (6.8-13.5) | 10.9 (1.4-16.9) | .01 | 9.5 (7-13.5) | 1.00 |
| Median WBC (range), × 109/L | 8.0 (2.5-96.1) | 13.3 (1.3-288.6) | .009 | 5 (1.5-13.1) | .007 |
| Median ANC (range), × 109/L | 3.3 (0.4-54.7) | 6.5 (0.0-155.6) | .009 | 2.7 (0.4-9.4) | .14 |
| Median AMC (range), × 109/L | 1.6 (1.2-11.5) | 2.7 (1-84.0) | .007 | 0.4 (0-1.0) | .005 |
| Median platelets (range), × 109/L | 138.0 (12-840) | 98.0 (2-1945) | .006 | 259.0 (13-599) | .03 |
| Presence of IMCs | 16 (41.0) | 478 (60.4) | .06 | NA | .005 |
| Median PB blast (range), % | 0 (0-3) | 0 (0-19) | .07 | 0 (0-0) | .009 |
| Median BM blast (range), % | 3 (0-16) | 3 (0-19) | .9 | 1 (0-4) | .004 |
| Presence of RSs* | 15/17 (88) | 68/482 (14) | <.001 | 83 (100) | 1.00 |
| Median VAF SF3B1 (range), % | 40.5 (8-48) | NA | NA | 41 (9-49) | 1.00 |
| Total no. of evaluable patients with FAB CMML subtypes | 40 | 817 | .04 | NA | NA |
| dCMML | 30 (75) | 399 (48.8) | NA | ||
| pCMML | 10 (25) | 418 (51.2) | NA | ||
| Total no. of evaluable patients with WHO 2016 CMML subtypes | 39 | 778 | .25 | NA | NA |
| CMML-0 | 29 (74.4) | 461 (59.3) | NA | ||
| CMML-1 | 7 (17.9) | 184 (23.7) | NA | ||
| CMML-2 | 3 (7.7) | 133 (17.1) | NA | ||
| Total no. of evaluable patients with CPSS-Mol cytogenetic risk stratification | 39 | 752 | .03 | 83 | 1.00 |
| Low | 29 (74.4) | 555 (73.8) | 66 (79.5) | ||
| Intermediate | 9 (23.1) | 85 (11.3) | 13 (15.7) | ||
| High | 1 (2.6) | 112 (14.9) | 4 (4.8) | ||
| Total no. of evaluable patients with NGS analysis | 40 | 567 | 83 | ||
| Epigenetic regulators | |||||
| TET2 | 17 (42.5) | 295 (52.0) | .39 | 21 (25.6) | .15 |
| IDH1 | 2 (5.0) | 5 (0.9) | .14 | 0 (0) | .23 |
| IDH2 | 2 (5.0) | 29 (5.1) | 1.00 | 1 (1.2) | .50 |
| DNMT3A | 7 (17.5) | 34 (6.0) | .05 | 16 (19.3) | 1.00 |
| Chromatin regulators | |||||
| ASXL1 | 4 (10.0) | 277 (48.9) | .03 | 11 (13.3) | 1.00 |
| EZH2 | 1 (2.5) | 45 (7.9) | .50 | 2 (2.4) | 1.00 |
| Transcription factor | |||||
| RUNX1 | 8 (20.0) | 78 (13.8) | .41 | 2 (2.4) | .007 |
| Spliceosome component genes | |||||
| SRSF2 | 5 (12.5) | 253 (44.6) | .02 | 2 (2.4) | .09 |
| U2AF1 | 0 (0) | 42 (7.4) | .18 | 0 (0) | 1.00 |
| ZRSR2 | 1 (2.5) | 36 (6.3) | .66 | NA | NA |
| Cell signaling | |||||
| NRAS | 5 (12.5) | 90 (15.9) | .72 | NA | NA |
| KRAS | 0/17 (0) | 19/313 (6.1) | .75 | NA | NA |
| CBL | 3 (7.5) | 88 (15.5) | .28 | 2 (2.4) | .62 |
| PTPN11 | 0/17 (0) | 9/313 (2.9) | .66 | NA | NA |
| JAK2 | 7 (17.5) | 40 (7.1) | .03 | 1 (1.2) | .01 |
| CSF3R | 0/17 (0) | 4/313 (1.3) | .76 | 3 (3.6) | 1.00 |
| KIT | 1 (2.5) | 24 (4.2) | .90 | NA | NA |
| MPL | 0 (0) | 5 (0.9) | .92 | NA | NA |
| CALR | 0/17 (0) | 1/313 (0.3) | .92 | NA | NA |
| Tumor suppressor gene | |||||
| TP53 | 1 (2.5) | 16 (2.8) | 1.00 | 3 (3.6) | 1.00 |
| Other | |||||
| SETBP1 | 0 (0) | 62 (10.9) | .10 | 2 (2.4) | 1.00 |
| No. of assessable patients for stratification by the Mayo Molecular Model | 40 | 809 | .02 | NA | NA |
| Low risk | 6 (15.0) | 93 (11.5) | NA | ||
| Intermediate-1 risk | 20 (50.0) | 265 (32.8) | NA | ||
| Intermediate-2 risk | 12 (30.0) | 237 (29.3) | NA | ||
| High risk | 2 (5.0) | 214 (26.5) | NA | ||
| No. of assessable patients for stratification by the GFM Model | 40 | 809 | .04 | NA | NA |
| Low risk | 27 (67.5) | 358 (44.3) | NA | ||
| Intermediate risk | 11 (27.5) | 320 (39.6) | NA | ||
| High risk | 2 (5.0) | 131 (16.2) | NA | ||
| No. of assessable patients for stratification by the IPSS-R | 40 | 748 | .14 | 83 | .43 |
| Very low | 7 (17.5) | 171 (22.9) | 26 (31.3) | ||
| Low | 23 (57.5) | 274 (36.6) | 46 (55.4) | ||
| Intermediate | 5 (12.5) | 174 (23.3) | 7 (8.4) | ||
| High | 5 (12.5) | 88 (11.8) | 4 (4.8) | ||
| Very high | 0 (0.0) | 41 (5.5) | 0 (0.0) | ||
| Deaths | 18 (45.0) | 461 (56.2) | — | 56 (67.5) | — |
| Leukemic transformation | 6 (15.0) | 159 (19.4) | — | 2 (2.4) | — |
All data are no. (%) unless otherwise specified. Bold indicates statistically significant P values (P < .05) provided only if data are available for all 3 cohorts.
AMC, absolute monocyte count; ANC, absolute neutrophil count; CPSS-Mol, Clinical/Molecular CMML-Specific Prognostic Scoring System; dCMML, dysplastic CMML; FAB, French-American-British; GFM, Groupe Francophone des Myelodyplasies; IMC, immature myeloid cell; IPSS-R, Revised International Prognostic Scoring System; NA, not available; pCMML, proliferative CMML.
Sideroblasts were evaluable in 17 SF3B1 mutant CMML patients and 482 SF3B1 wildtype CMML patients, of whom, 15 and 68 had RS, respectively.