Table 1 Baseline clinical and laboratory characteristics, and co-mutational patterns of TET2 in wild-type and mutated configurations in 536 informative patients with chronic myelomonocytic leukemia.
TET2 wild-type N = 221 (41%) | One TET2 mutation N = 148 (28%) | Two TET2 mutations N = 153 (29%) | ≥3 TET2 mutations N = 14 (2%) | P value overall | P value one vs. two TET2 mutations | |
|---|---|---|---|---|---|---|
Age in years, median (range) | 70 (18–92) | 72 (47–91) | 72 (2–88) | 73.5 (62–90) | 0.03 | 0.73 |
Male sex | 160 (72) | 109 (74) | 103 (67) | 6 (43) | 0.09 | 0.22 |
Dominant allele frequency (%), median, range | NA | 46 (3-100) | 45 (25–92) | 42 (14–49) | 0.01 | 0.14 |
Dominant allele frequency ≥50, n (%) | NA | 45 (30) | 16 (10) | 0 (0) | <0.01 | <0.01 |
Location of dominant mutation, n (%) | ||||||
C-Terminal | NA | 89 (60) | 63 (41) | 8 (57) | <0.01 | <0.01 |
N-Terminal | NA | 59 (40) | 90 (59) | 6(43) | ||
Type of dominant mutation, n (%) | ||||||
Truncating | NA | 127 (86) | 136 (89) | 13 (93) | 0.59 | 0.42 |
Non-truncating | NA | 21 (14) | 17 (11) | 1 (7) | ||
CMML WHO classification, n (%) | ||||||
CMML1 | 185 (84) | 137 (92) | 143 (93) | 13 (93) | <0.01 | 0.76 |
CMML2 | 36 (16) | 11 (8) | 10 (7) | 1 (7) | ||
Transfusion requiring, n (%) | 52 (24) | 18 (12) | 14 (9) | 2 (14) | <0.01 | 0.39 |
Hemoglobin g/dl, median | 10.6 (5.3–16.9) | 11.8 (6–17.6) | 11.9 (7–16) | 11.5 (5.9–13.7) | <0.01 | 0.89 |
Platelets ×109/L, median | 124 (6–1257) | 91 (10–584) | 95 (6 -600) | 100 (38–340) | <0.01 | 0.76 |
Platelets <100 × 109/L, n (%) | 83 (38) | 87 (59) | 83 (54) | 7 (50) | <0.01 | 0.42 |
Leukocytes ×109/L, median | 13.2 (2–183.3) | 9.6 (2.3–96) | 9.3 (2.1–81) | 8.5 (3.2–81.4) | <0.01 | 0.33 |
Leukocytes ≥13 × 109/L, n (%) | 111 (50) | 56 (38) | 54 (35) | 5 (36) | 0.02 | 0.64 |
Absolute neutrophil count ×109/L, median | 6.5 (0.1–68.4) | 4.3 (0.3–55) | 4.7 (0.3–42.3) | 3.8 (0.7–57) | <0.01 | 0.50 |
Absolute monocyte count ×109/L, median | 2.2 (0.1–62.3) | 2.1 (0.4–26) | 2 (0.3–32) | 1.9 (0.6–12) | 0.29 | 0.33 |
Blood blast %, median (range) | 0 (0–17) | 0 (0–7) | 0 (0–13) | 0 (0–1) | <0.01 | 0.86 |
Blood blast ≥2%, n (%) | 56 (25) | 12 (8) | 10 (7) | 0 (0) | <0.01 | 0.60 |
Bone marrow blast %, mean | 3 (0–19) | 2 (0–19) | 3 (0–19) | 2.5 (0–17) | 0.11 | 0.81 |
Bone marrow blast ≥10%, n (%) | 29 (13) | 7 (5) | 8 (5) | 1 (7) | 0.01 | 0.84 |
Cytogenetics, n (%): | ||||||
1. Normal karyotype | 155 (70) | 118 (80) | 132 (87) | 12 (86) | <0.01 | 0.12 |
Abnormal karyotype | 65 (30) | 29 (20) | 20 (13) | 2 (14) | ||
2. Complex karyotype | 10 (5) | 2 (1) | 1 (0.6) | 1 (7) | 0.05 | 0.09 |
3. Del(4q) | 0 (0) | 4 (3) | 0 (0) | 0(0) | 0.02 | 0.02 |
Anemia severity*; n (%) | ||||||
Moderate anemia | 55 (25) | 28 (19) | 34 (22) | 1 (7) | <0.01 | 0.26 |
Severe anemia | 53 (24) | 21 (14) | 13 (9) | 2 (14) | ||
Blast-transformation, n (%) | 47 (21) | 36 (24) | 22 (14) | 4 (29) | 0.12 | 0.03 |
Allogeneic stem cell transplant, n (%) | 54 (24) | 21 (14) | 28 (18) | 1 (7) | 0.04 | 0.33 |
Deaths, n (%) | 136 (62) | 80 (54) | 70 (46) | 10 (71) | 0.01 | 0.14 |
Co-mutations | ||||||
ASXL1 | 130 (58) | 68 (46) | 44 (29) | 5 (36) | <0.01 | <0.01 |
SRSF2 | 85 (39) | 86 (58) | 81 (53) | 5 (36) | <0.01 | 0.36 |
RUNX1 | 54 (24) | 30 (20) | 23 (15) | 2 (14) | 0.14 | 0.23 |
KRAS | 35 (16) | 10 (7) | 21 (14) | 3 (21) | 0.03 | 0.04 |
NRAS | 32 (14) | 22 (15) | 19 (12) | 3 (21) | 0.79 | 0.53 |
SETBP1 | 32 (14) | 7 (5) | 1 (0.6) | 0 (0) | <0.01 | 0.02 |
IDH2 | 25 (11) | 1 (0.7) | 0 (0) | 0 (0) | <0.01 | 0.23 |
CBL | 24 (11) | 14 (9) | 25 (16) | 3 (21) | 0.20 | 0.07 |
U2AF1 | 22 (10) | 7 (5) | 7 (5) | 0 (0) | 0.05 | 0.94 |
DNMT3A | 21 (10) | 11 (7) | 7 (5) | 0 (0) | 0.13 | 0.29 |
JAK2 | 14 (6) | 15 (10) | 10 (7) | 0 (0) | 0.24 | 0.25 |
BCOR | 14 (6) | 1 (0.7) | 1 (0.6) | 0 (0) | <0.01 | 0.98 |
EZH2 | 13 (6) | 11 (7) | 11 (7) | 1 (7) | 0.94 | 0.93 |
PTPN11 | 12 (6) | 6 (4) | 5 (3) | 0 (0) | 0.50 | 0.71 |
STAG2 | 12 (6) | 3 (2) | 2 (1) | 0 (0) | 0.06 | 0.62 |
SF3B1 | 10 (5) | 7 (5) | 5 (3) | 0 (0) | 0.63 | 0.51 |
TP53 | 8 (3) | 3 (2) | 2 (1) | 0 (0) | 0.40 | 0.62 |
KIT | 8 (4) | 2 (1) | 6 (4) | 2 (14) | 0.13 | 0.15 |
PHF6 | 7 (3) | 12 (8) | 19 (12) | 3 (21) | <0.01 | 0.21 |
IDH1 | 7 (3) | 1 (0.7) | 2 (1) | 0 (0) | 0.25 | 0.57 |
ETNK1 | 6 (3) | 3 (2) | 2 (1) | 0 (0) | 0.67 | 0.62 |
FLT3 | 6 (3) | 3 (2) | 0 (0) | 1 (7) | 0.05 | 0.04 |
ZRSR2 | 6 (3) | 11 (7) | 13 (8) | 2 (14) | 0.04 | 0.73 |
ETV6 | 5 (2) | 3 (2) | 0 (0) | 0 (0) | 0.10 | 0.04 |
CSF3R | 4 (2) | 1 (0.7) | 0 (0) | 0 (0) | 0.19 | 0.23 |
CUX1 | 4 (2) | 2 (1) | 1 (0.6) | 0 (0) | 0.70 | 0.53 |
WT1 | 2 (1) | 0 (0) | 1 (0.6) | 0 (0) | 0.06 | 0.24 |
SH2B3 | 2 (1) | 2 (1) | 5 (3) | 0 (0) | 0.34 | 0.26 |
NPM1 | 2 (1) | 1 (0.7) | 0 (0) | 0 (0) | 0.50 | 0.23 |
MPL | 2 (1) | 2 (1) | 5 (3) | 0 (0) | 0.34 | 0.26 |
CEBPA | 2 (1) | 0 (0) | 1 (0.6) | 0 (0) | 0.52 | 0.24 |
SUZ12 | 0 (0) | 1 (0.7) | 0 (0) | 0 (0) | 0.46 | 0.23 |
BRAF | 0 (0) | 1 (0.7) | 1 (0.6) | 1 (7) | 0.51 | 0.98 |
CALR | 0 (0) | 0 (0) | 3 (2) | 0 (0) | 0.06 | 0.04 |
