Clinical and laboratory characteristics of study population
| Variables . | ASXL1 WT, N = 214 . | ASXL1 G646Wfsx, N = 33 . | ASXL1 other mutations, N = 86 . | P ASXL1 WT vs ASXL1 G646W . | P ASXL1 WT vs ASXL1 other mutations . | P ASXL1 G646W vs ASXL1 other mutations . |
|---|---|---|---|---|---|---|
| n (%) or median (range) . | n (%) or median (range) . | n (%) or median (range) . | ||||
| Follow-up, y | 5.6 (0.5-33.1) | 3.2 (0.6-8.6) | 3.1 (0.2-25.1) | .004 | .008 | .57 |
| Prefibrotic PMF diagnosis | 105 (49.1) | 10 (30.3) | 24 (27.9) | .04 | .001 | .76 |
| Males | 128 (59.8) | 25 (75.8) | 65 (75.6) | .08 | .01 | .98 |
| Age, y | 61.1 (17.7-90.3) | 67.4 (48.6-87.3) | 63.7 (28.4-89.8) | .01 | .12 | .13 |
| Age >65 y | 90 (42.1) | 21 (63.6) | 36 (41.9) | .02 | .97 | .03 |
| Hemoglobin, g/L | 12.0 (4.7-16.0) | 11.0 (6.2-15.0) | 11.5 (5.0-16.5) | .14 | .08 | .90 |
| Hemoglobin, <100 g/L | 48 (22.4) | 9 (27.3) | 26 (30.2) | .54 | .15 | .75 |
| Leukocytes, ×109/L | 8.5 (1.4-106.1) | 11.7 (3.5-250.0) | 10.7 (1.5-90.8) | .02 | .10 | .39 |
| Leukocytes, >25 × 109/L | 14 (6.5) | 7 (21.2) | 17 (19.8) | .005 | .001 | .86 |
| Platelets, ×109/L | 359 (10-1563) | 236 (38-1344) | 278 (37-1252) | .04 | .06 | .33 |
| Platelets, <100 × 109/L | 23 (10.7) | 6 (18.2) | 8 (9.3) | .22 | .71 | .18 |
| Circulating blasts, ≥2% | 13 (6.1) | 9 (27.3) | 28 (32.6) | <.0001 | <.0001 | .56 |
| LDH > UNL, n = 211 | 122 (90.4) | 19 (86.4) | 48 (88.9) | .56 | .76 | .76 |
| Splenomegaly >10 cm from LCM | 39 (18.4) | 13 (39.4) | 29 (34.1) | .03 | .003 | .74 |
| BM fibrosis grade | .05 | <.0001 | .78 | |||
| G1 | 84 (41.4) | 8 (26.7) | 22 (27.2) | |||
| G2/G3 | 97 (45.3) | 20 (60.6) | 56 (65.1) | |||
| Constitutional symptoms | 63 (29.4) | 17 (51.5) | 39 (45.3) | .01 | .01 | .55 |
| Karyotype information, n = 264 | ||||||
| Abnormal cytogenetics | 45 (29.8) | 10 (41.7) | 27 (45.8) | .25 | .03 | .73 |
| Unfavorable karyotype* | 22 (14.7) | 8 (33.3) | 18 (30.5) | .02 | .009 | .81 |
| IPSS | <.0001 | <.0001 | .23 | |||
| Low | 77 (36.0) | 2 (6.1) | 17 (19.8) | |||
| Intermediate 1 | 72 (33.6) | 11 (33.3) | 22 (25.6) | |||
| Intermediate 2 | 39 (18.2) | 7 (21.2) | 22 (25.6) | |||
| High | 26 (12.1) | 13 (39.4) | 25 (29.1) | |||
| MIPSS70 | <.0001 | <.0001 | .85 | |||
| Low | 50 (23.4) | 0 (0.0) | 0 (0.0) | |||
| Intermediate | 92 (43.0) | 6 (18.2) | 17 (19.8) | |||
| High | 72 (33.6) | 27 (81.8) | 69 (80.2) | |||
| Driver mutation | ||||||
| JAK2V617F | 142 (66.4) | 19 (57.6) | 52 (60.5) | .27 | .35 | .68 |
| CALR type1 | 29 (13.6) | 1 (3.0) | 13 (15.1) | .04 | .63 | .04 |
| CALR type2 | 12 (5.6) | 1 (3.0) | 6 (7.0) | .57 | .96 | .60 |
| MPLW515x | 10 (4.7) | 2 (6.1) | 4 (4.7) | .99 | .63 | .75 |
| Triple negative† | 21 (9.8) | 10 (30.3) | 11 (12.8) | .001 | .45 | .02 |
| Acute leukemia progression | 14 (6.5) | 9 (27.3) | 12 (14.0) | <.0001 | .04 | .09 |
| Death | 67 (31.3) | 26 (78.8) | 57 (66.3) | <.0001 | <.0001 | .18 |
| HMR | 26 (12.1) | 33 (100) | 86 (100) | <.0001 | <.0001 | .99 |
| HMR ≥2 | 3 (1.4) | 19 (57.6) | 35 (40.7) | <.0001 | <.0001 | .98 |
| EZH2 mut | 9 (4.2) | 9 (27.3) | 17 (19.8) | <.0001 | <.0001 | .37 |
| SRSF2 mut | 14 (6.5) | 10 (30.3) | 16 (18.6) | <.0001 | .02 | .17 |
| IDH1/2 mut | 6 (2.8) | 0 (0.0) | 6 (7.0) | .33 | .09 | .12 |
| CBL mut | 3 (1.4) | 5 (15.2) | 10 (11.6) | <.0001 | <.0001 | .65 |
| TET2 mut | 39 (18.2) | 9 (27.3) | 8 (9.3) | .36 | .03 | .02 |
| DNMT3A mut | 12 (5.6) | 1 (3.0) | 2 (2.3) | .46 | .18 | .85 |
| SH3B3 mut | 5 (2.3) | 0 (0.0) | 5 (5.8) | .32 | .19 | .14 |
| TP53 mut | 6 (2.8) | 1 (3.0) | 6 (7.0) | .92 | .15 | .38 |
| U2AF1 mut | 2 (0.9) | 5 (15.2) | 7 (8.1) | <.0001 | .002 | .31 |
| NRAS mut, n = 233 | 3 (2.1) | 7 (25.9) | 9 (14.3) | <.0001 | .001 | .19 |
| KRAS mut, n = 233 | 2 (1.4) | 2 (7.7) | 4 (6.3) | .05 | .06 | .80 |
| SF3B1 mut, n = 238 | 12 (8.2) | 0 (0.0) | 4 (6.2) | .12 | .60 | .19 |
| RUNX1 mut, n = 235 | 3 (2.1) | 2 (7.4) | 2 (3.1) | .13 | .65 | .36 |
| cKIT mut, n = 235 | 1 (0.7) | 0 (0.0) | 0 (0.0) | .66 | .50 |
| Variables . | ASXL1 WT, N = 214 . | ASXL1 G646Wfsx, N = 33 . | ASXL1 other mutations, N = 86 . | P ASXL1 WT vs ASXL1 G646W . | P ASXL1 WT vs ASXL1 other mutations . | P ASXL1 G646W vs ASXL1 other mutations . |
|---|---|---|---|---|---|---|
| n (%) or median (range) . | n (%) or median (range) . | n (%) or median (range) . | ||||
| Follow-up, y | 5.6 (0.5-33.1) | 3.2 (0.6-8.6) | 3.1 (0.2-25.1) | .004 | .008 | .57 |
| Prefibrotic PMF diagnosis | 105 (49.1) | 10 (30.3) | 24 (27.9) | .04 | .001 | .76 |
| Males | 128 (59.8) | 25 (75.8) | 65 (75.6) | .08 | .01 | .98 |
| Age, y | 61.1 (17.7-90.3) | 67.4 (48.6-87.3) | 63.7 (28.4-89.8) | .01 | .12 | .13 |
| Age >65 y | 90 (42.1) | 21 (63.6) | 36 (41.9) | .02 | .97 | .03 |
| Hemoglobin, g/L | 12.0 (4.7-16.0) | 11.0 (6.2-15.0) | 11.5 (5.0-16.5) | .14 | .08 | .90 |
| Hemoglobin, <100 g/L | 48 (22.4) | 9 (27.3) | 26 (30.2) | .54 | .15 | .75 |
| Leukocytes, ×109/L | 8.5 (1.4-106.1) | 11.7 (3.5-250.0) | 10.7 (1.5-90.8) | .02 | .10 | .39 |
| Leukocytes, >25 × 109/L | 14 (6.5) | 7 (21.2) | 17 (19.8) | .005 | .001 | .86 |
| Platelets, ×109/L | 359 (10-1563) | 236 (38-1344) | 278 (37-1252) | .04 | .06 | .33 |
| Platelets, <100 × 109/L | 23 (10.7) | 6 (18.2) | 8 (9.3) | .22 | .71 | .18 |
| Circulating blasts, ≥2% | 13 (6.1) | 9 (27.3) | 28 (32.6) | <.0001 | <.0001 | .56 |
| LDH > UNL, n = 211 | 122 (90.4) | 19 (86.4) | 48 (88.9) | .56 | .76 | .76 |
| Splenomegaly >10 cm from LCM | 39 (18.4) | 13 (39.4) | 29 (34.1) | .03 | .003 | .74 |
| BM fibrosis grade | .05 | <.0001 | .78 | |||
| G1 | 84 (41.4) | 8 (26.7) | 22 (27.2) | |||
| G2/G3 | 97 (45.3) | 20 (60.6) | 56 (65.1) | |||
| Constitutional symptoms | 63 (29.4) | 17 (51.5) | 39 (45.3) | .01 | .01 | .55 |
| Karyotype information, n = 264 | ||||||
| Abnormal cytogenetics | 45 (29.8) | 10 (41.7) | 27 (45.8) | .25 | .03 | .73 |
| Unfavorable karyotype* | 22 (14.7) | 8 (33.3) | 18 (30.5) | .02 | .009 | .81 |
| IPSS | <.0001 | <.0001 | .23 | |||
| Low | 77 (36.0) | 2 (6.1) | 17 (19.8) | |||
| Intermediate 1 | 72 (33.6) | 11 (33.3) | 22 (25.6) | |||
| Intermediate 2 | 39 (18.2) | 7 (21.2) | 22 (25.6) | |||
| High | 26 (12.1) | 13 (39.4) | 25 (29.1) | |||
| MIPSS70 | <.0001 | <.0001 | .85 | |||
| Low | 50 (23.4) | 0 (0.0) | 0 (0.0) | |||
| Intermediate | 92 (43.0) | 6 (18.2) | 17 (19.8) | |||
| High | 72 (33.6) | 27 (81.8) | 69 (80.2) | |||
| Driver mutation | ||||||
| JAK2V617F | 142 (66.4) | 19 (57.6) | 52 (60.5) | .27 | .35 | .68 |
| CALR type1 | 29 (13.6) | 1 (3.0) | 13 (15.1) | .04 | .63 | .04 |
| CALR type2 | 12 (5.6) | 1 (3.0) | 6 (7.0) | .57 | .96 | .60 |
| MPLW515x | 10 (4.7) | 2 (6.1) | 4 (4.7) | .99 | .63 | .75 |
| Triple negative† | 21 (9.8) | 10 (30.3) | 11 (12.8) | .001 | .45 | .02 |
| Acute leukemia progression | 14 (6.5) | 9 (27.3) | 12 (14.0) | <.0001 | .04 | .09 |
| Death | 67 (31.3) | 26 (78.8) | 57 (66.3) | <.0001 | <.0001 | .18 |
| HMR | 26 (12.1) | 33 (100) | 86 (100) | <.0001 | <.0001 | .99 |
| HMR ≥2 | 3 (1.4) | 19 (57.6) | 35 (40.7) | <.0001 | <.0001 | .98 |
| EZH2 mut | 9 (4.2) | 9 (27.3) | 17 (19.8) | <.0001 | <.0001 | .37 |
| SRSF2 mut | 14 (6.5) | 10 (30.3) | 16 (18.6) | <.0001 | .02 | .17 |
| IDH1/2 mut | 6 (2.8) | 0 (0.0) | 6 (7.0) | .33 | .09 | .12 |
| CBL mut | 3 (1.4) | 5 (15.2) | 10 (11.6) | <.0001 | <.0001 | .65 |
| TET2 mut | 39 (18.2) | 9 (27.3) | 8 (9.3) | .36 | .03 | .02 |
| DNMT3A mut | 12 (5.6) | 1 (3.0) | 2 (2.3) | .46 | .18 | .85 |
| SH3B3 mut | 5 (2.3) | 0 (0.0) | 5 (5.8) | .32 | .19 | .14 |
| TP53 mut | 6 (2.8) | 1 (3.0) | 6 (7.0) | .92 | .15 | .38 |
| U2AF1 mut | 2 (0.9) | 5 (15.2) | 7 (8.1) | <.0001 | .002 | .31 |
| NRAS mut, n = 233 | 3 (2.1) | 7 (25.9) | 9 (14.3) | <.0001 | .001 | .19 |
| KRAS mut, n = 233 | 2 (1.4) | 2 (7.7) | 4 (6.3) | .05 | .06 | .80 |
| SF3B1 mut, n = 238 | 12 (8.2) | 0 (0.0) | 4 (6.2) | .12 | .60 | .19 |
| RUNX1 mut, n = 235 | 3 (2.1) | 2 (7.4) | 2 (3.1) | .13 | .65 | .36 |
| cKIT mut, n = 235 | 1 (0.7) | 0 (0.0) | 0 (0.0) | .66 | .50 |
Bold values in the table body indicate significant correlations at the level of 0.05.
BM, bone marrow; HMR, high-molecular-risk category, points to the presence of any 1 mutation in ASXL1, EZH2, SRSF2, IDH1/2; HMR ≥ 2, the presence of 2 or more mutated genes among ASXL1, EZH2, SRSF2, IDH1/2 (2 or more mutations in the same gene are counted as 1); IPSS, International Prognostic Scoring System; LDH, lactate dehydrogenase; LCM, left costal margin; MIPSS70, mutation-enhanced International Prognostic Scoring System for transplantation-age patients with primary myelofibrosis; MPLW515x, any mutation occurring at MPL codon 515; mut, mutation; PMF, primary myelofibrosis; UNL, upper normal limit; WT, wild type.
Unfavorable karyotype indicates any abnormal karyotype other than normal karyotype or sole abnormalities of 20q−, 13q−, +9, chromosome 1 translocation/duplication, −Y or sex chromosome abnormality other than −Y.
Triple negative indicates patients who lacked driver mutation.