Clinicopathological details for patients with AML/MDS with LP/P variants in DDX41
| . | Patients with MDS . | Patients with AML . | ||||||
|---|---|---|---|---|---|---|---|---|
| Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020 . | P . | |
| Male/female (ratio) | 1824/1041 (1.8) | 84/24 (3.5) | 1713/1007 (1.7) | NS | 1243/914 (1.4) | 79/27 (2.9) | 1145/875 (1.3) | <.001 |
| Median age, y (range) | 76 (15-96) | 72 (47-92) | 76 (15-96) | NS | 72 (4-97) | 72 (47-93) | 71.4 (4-97) | NS |
| . | Patients with MDS . | Patients with AML . | ||||||
|---|---|---|---|---|---|---|---|---|
| Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020 . | P . | |
| Male/female (ratio) | 1824/1041 (1.8) | 84/24 (3.5) | 1713/1007 (1.7) | NS | 1243/914 (1.4) | 79/27 (2.9) | 1145/875 (1.3) | <.001 |
| Median age, y (range) | 76 (15-96) | 72 (47-92) | 76 (15-96) | NS | 72 (4-97) | 72 (47-93) | 71.4 (4-97) | NS |
| Cytomorphological diagnosis (WHO 2017), n (%) . | Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020) . | P . |
|---|---|---|---|---|---|---|---|---|
| MDS | 337 (11.8) | 18 (16.7) | 311 (11.4) | NS | ||||
| MDS with isolated del(5q) | 113 (3.9) | 1 (0.9) | 111 (4.1) | NS | ||||
| MDS-EB-1 | 798 (27.9) | 27 (25.0) | 758 (27.9) | NS | ||||
| MDS-EB-2 | 591 (20.6) | 44 (40.7) | 537 (19.7) | <.001 | ||||
| MDS-MLD | 388 (13.5) | 15 (13.9) | 371 (13.6) | NS | ||||
| MDS-RS-MLD | 568 (19.8) | 3 (2.8) | 563 (20.7) | <.001 | ||||
| MDS-SLD | 10 (0.3) | 0 | 10 (0.4) | NS | ||||
| MDS-RS-SLD | 46 (1.6) | 0 | 45 (1.7) | NS | ||||
| MDS-U | 14 (0.5) | 0 | 14 (0.5) | NS | ||||
| Acute monoblastic/monocytic leukemia | 56 (2.6) | 0 | 56 (2.8) | NS | ||||
| Acute myelomonocytic leukemia | 158 (7.3) | 1 (0.9) | 153 (7.6) | NS | ||||
| AML | 368 (17.1) | 3 (2.8) | 360 (17.8) | <.001 | ||||
| AML with CBFB::MYH11 | 31 (1.4) | 0 | 30 (1.5) | NS | ||||
| AML with maturation | 513 (23.8) | 44 (41.5) | 462 (22.9) | <.001 | ||||
| AML with minimal differentiation | 178 (8.3) | 20 (18.9) | 156 (7.7) | <.001 | ||||
| AML with myelodysplasia-related changes | 277 (12.8) | 11 (10.4) | 263 (13.0) | NS | ||||
| AML without maturation | 360 (16.7) | 12 (11.3) | 341 (16.9) | NS | ||||
| s-AML arising from previous MDS | 216 (10.0) | 15 (14.2) | 199 (9.9) | NS |
| Cytomorphological diagnosis (WHO 2017), n (%) . | Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020) . | P . |
|---|---|---|---|---|---|---|---|---|
| MDS | 337 (11.8) | 18 (16.7) | 311 (11.4) | NS | ||||
| MDS with isolated del(5q) | 113 (3.9) | 1 (0.9) | 111 (4.1) | NS | ||||
| MDS-EB-1 | 798 (27.9) | 27 (25.0) | 758 (27.9) | NS | ||||
| MDS-EB-2 | 591 (20.6) | 44 (40.7) | 537 (19.7) | <.001 | ||||
| MDS-MLD | 388 (13.5) | 15 (13.9) | 371 (13.6) | NS | ||||
| MDS-RS-MLD | 568 (19.8) | 3 (2.8) | 563 (20.7) | <.001 | ||||
| MDS-SLD | 10 (0.3) | 0 | 10 (0.4) | NS | ||||
| MDS-RS-SLD | 46 (1.6) | 0 | 45 (1.7) | NS | ||||
| MDS-U | 14 (0.5) | 0 | 14 (0.5) | NS | ||||
| Acute monoblastic/monocytic leukemia | 56 (2.6) | 0 | 56 (2.8) | NS | ||||
| Acute myelomonocytic leukemia | 158 (7.3) | 1 (0.9) | 153 (7.6) | NS | ||||
| AML | 368 (17.1) | 3 (2.8) | 360 (17.8) | <.001 | ||||
| AML with CBFB::MYH11 | 31 (1.4) | 0 | 30 (1.5) | NS | ||||
| AML with maturation | 513 (23.8) | 44 (41.5) | 462 (22.9) | <.001 | ||||
| AML with minimal differentiation | 178 (8.3) | 20 (18.9) | 156 (7.7) | <.001 | ||||
| AML with myelodysplasia-related changes | 277 (12.8) | 11 (10.4) | 263 (13.0) | NS | ||||
| AML without maturation | 360 (16.7) | 12 (11.3) | 341 (16.9) | NS | ||||
| s-AML arising from previous MDS | 216 (10.0) | 15 (14.2) | 199 (9.9) | NS |
| CBC parameters, n . | Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020) . | P . |
|---|---|---|---|---|---|---|---|---|
| Median WBC count, × 103/μL (range) | 3.4 (0.1-117.4); 2160 | 2.2 (0.8-9.1); 86 | 3.5 (0.1-117.4); 2045 | <.001 | 5.9 (0.1-493.2); 1778 | 1.8 (0.6-104.2); 87 | 6.9 (0.1-493.2); 1671 | <.001 |
| Median Hb level, g/dL (range) | 9.4 (2.8-17.0); 2089 | 9.7 (5.5-14.5); 84 | 9.4 (2.8-17.0); 1977 | NS | 8.9 (1.5-17.7); 1658 | 9.6 (2.9-14.6); 83 | 8.8 (1.5-17.7); 1556 | <.001 |
| Median platelet count, × 103/μL (range) | 113.0 (1.0-1,391.0); 2077 | 96.0 (12.0-336.0); 83 | 114.0 (1.0-1391.0); 1966 | <.001 | 70.0 (1.0-1,505.0); 1660 | 64.0 (7.0-256.0); 85 | 70.0 (1.0-1505.0); 1556 | <.001 |
| Median blasts bone marrow, % (range) | 4.5 (0-19.5); 2670 | 8.0 (0-19.5); 104 | 4.5 (0-19.5); 2532 | <.001 | 46.0 (6.0-99.5); 1783 | 32.0 (20.0-89.5); 104 | 48.0 (6.0-99.5); 1650 | <.001 |
| CBC parameters, n . | Total cohort (n = 2865) . | DDX41 germ line LP/P (n = 108) . | DDX41-WT (n = 2720) . | P . | Total cohort (n = 2157) . | DDX41 germ line LP/P (n = 106) . | DDX41-WT (n = 2020) . | P . |
|---|---|---|---|---|---|---|---|---|
| Median WBC count, × 103/μL (range) | 3.4 (0.1-117.4); 2160 | 2.2 (0.8-9.1); 86 | 3.5 (0.1-117.4); 2045 | <.001 | 5.9 (0.1-493.2); 1778 | 1.8 (0.6-104.2); 87 | 6.9 (0.1-493.2); 1671 | <.001 |
| Median Hb level, g/dL (range) | 9.4 (2.8-17.0); 2089 | 9.7 (5.5-14.5); 84 | 9.4 (2.8-17.0); 1977 | NS | 8.9 (1.5-17.7); 1658 | 9.6 (2.9-14.6); 83 | 8.8 (1.5-17.7); 1556 | <.001 |
| Median platelet count, × 103/μL (range) | 113.0 (1.0-1,391.0); 2077 | 96.0 (12.0-336.0); 83 | 114.0 (1.0-1391.0); 1966 | <.001 | 70.0 (1.0-1,505.0); 1660 | 64.0 (7.0-256.0); 85 | 70.0 (1.0-1505.0); 1556 | <.001 |
| Median blasts bone marrow, % (range) | 4.5 (0-19.5); 2670 | 8.0 (0-19.5); 104 | 4.5 (0-19.5); 2532 | <.001 | 46.0 (6.0-99.5); 1783 | 32.0 (20.0-89.5); 104 | 48.0 (6.0-99.5); 1650 | <.001 |
| Cytogenetics, n (%) . | Total cohort (n = 2637) . | DDX41 germ line LP/P (n = 96) . | DDX41-WT (n = 2509) . | P . | Total cohort (n = 1971) . | DDX41 germ line LP/P (n = 97) . | DDX41-WT (n = 1848) . | P . |
|---|---|---|---|---|---|---|---|---|
| Normal karyotype | 1569 (59.5) | 79 (82.3) | 1467 (58.5) | <.001 | 928 (47.1) | 73 (75.3) | 837 (45.3) | <.001 |
| Aberrant karyotype | 1068 (40.5) | 17 (17.7) | 1042 (41.5) | 1043 (52.9) | 24 (24.7) | 1011 (54.7) | ||
| Trisomy 8 | 150 (5.7) | 1 (1.0) | 148 (5.9) | 131 (6.6) | 5 (5.2) | 126 (6.8) | ||
| chr7 aberration | 64 (2.4) | 0 | 64 (2.6) | 76 (3.9) | 1 (1.0) | 74 (4.0) | ||
| Loss of Y-chromosome | 109 (4.1) | 7 (7.3) | 100 (4.0) | 25 (1.3) | 1 (1.0) | 23 (1.2) | ||
| t(8;21)(q22;q22.1) | 1 (0.0) | 0 | 1 (0.0) | 27 (1.4) | 0 | 27 (1.5) | ||
| inv(16)(p13.1q22)/ t(16;16)(p13.1;q22) | 0 | 0 | 0 | 48 (2.4) | 0 | 47 (2.5) | ||
| del(5q) | 182 (6.9) | 3 (3.1) | 175 (7.0) | 52 (2.6) | 0 | 51 (2.8) | ||
| Complex | 240 (9.1) | 1 (1.0) | 238 (9.5) | 308 (15.6) | 7 (7.2) | 300 (16.2) | ||
| All other | 322 (12.2) | 5 (5.2) | 316 (12.6) | 376 (19.1) | 10 (10.3) | 363 (19.6) |
| Cytogenetics, n (%) . | Total cohort (n = 2637) . | DDX41 germ line LP/P (n = 96) . | DDX41-WT (n = 2509) . | P . | Total cohort (n = 1971) . | DDX41 germ line LP/P (n = 97) . | DDX41-WT (n = 1848) . | P . |
|---|---|---|---|---|---|---|---|---|
| Normal karyotype | 1569 (59.5) | 79 (82.3) | 1467 (58.5) | <.001 | 928 (47.1) | 73 (75.3) | 837 (45.3) | <.001 |
| Aberrant karyotype | 1068 (40.5) | 17 (17.7) | 1042 (41.5) | 1043 (52.9) | 24 (24.7) | 1011 (54.7) | ||
| Trisomy 8 | 150 (5.7) | 1 (1.0) | 148 (5.9) | 131 (6.6) | 5 (5.2) | 126 (6.8) | ||
| chr7 aberration | 64 (2.4) | 0 | 64 (2.6) | 76 (3.9) | 1 (1.0) | 74 (4.0) | ||
| Loss of Y-chromosome | 109 (4.1) | 7 (7.3) | 100 (4.0) | 25 (1.3) | 1 (1.0) | 23 (1.2) | ||
| t(8;21)(q22;q22.1) | 1 (0.0) | 0 | 1 (0.0) | 27 (1.4) | 0 | 27 (1.5) | ||
| inv(16)(p13.1q22)/ t(16;16)(p13.1;q22) | 0 | 0 | 0 | 48 (2.4) | 0 | 47 (2.5) | ||
| del(5q) | 182 (6.9) | 3 (3.1) | 175 (7.0) | 52 (2.6) | 0 | 51 (2.8) | ||
| Complex | 240 (9.1) | 1 (1.0) | 238 (9.5) | 308 (15.6) | 7 (7.2) | 300 (16.2) | ||
| All other | 322 (12.2) | 5 (5.2) | 316 (12.6) | 376 (19.1) | 10 (10.3) | 363 (19.6) |
P values are given for significant differences (P < .001) between patients with DDX41-WT and patients with germ line LP/P DDX41 variants. Patients carrying only somatic mutations or a germ line VUS in DDX41 are not listed separately but are included in the total cohort.
CBC, complete blood count; EB, excess blasts; NS, not significant; RS, ring sideroblasts; s-AML, secondary-acute myeloid leukaemia; SLD, single lineage dysplasia; WBC, white blood cell; WHO, World Health Organization.