Clinicopathologic characteristics of 23 patients with STAT3 SH2 domain variants
Age, y . | Sex . | NGS indication . | Specimen . | All somatic variants detected on NGS panel (VAF %) . | T-cell clonality* . | Splenomegaly . | WBCs, ×109/L . | Neutrophil count, ×109/L . | Lymphocyte count, ×109/L . | Hgb, g/dL . | Platelets, ×109/L . | Follow-up, mo† . |
---|---|---|---|---|---|---|---|---|---|---|---|---|
45 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (13.8) | Yes | No | 1.16 | 0.31 | 0.6 | 14.6 | 106 | 14.7 |
55 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (14.9)‡ | Yes | No | 3.27 | 0.97 | 1.81 | 14.0 | 212 | 4.2 |
51 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (19.4) | Yes | Yes | 4.6 | 1.15 | 3.04 | 11.4 | 187 | 13.0 |
69 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (2.3) | Yes | No | 3.23 | 1.36 | 1.54 | 9.5 | 51 | 24.5 |
STAT3 c.1165T>C p.T389A (10.7) | ||||||||||||
29 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (25.2) | Yes | Yes | 5.88 | 1.3 | 3.87 | 15.2 | 145 | 0 |
61 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (3.4) | Yes | Yes | 0.9 | 0.24 | 0.5 | 11.4 | 95 | 0 |
71 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (32.7) | Yes | No | 16.02 | 1.97 | 12.75 | 13.2 | 225 | 12.1 |
45 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (35.7) | Yes | No | 10.78 | 1.29 | 7.76 | 12.8 | 255 | 13.1 |
BRAF c.1781A>G p.D594G (4.7) | ||||||||||||
49 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (4.2) | Yes | No | 2.04 | 0.33 | 1 | 13.8 | 225 | 20.1 |
36 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.2) | Yes | No | 1.13 | 0.57 | 0.49 | 12.2 | 121 | 7.0 |
60 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.6) | Yes | No | 4.44 | 2.26 | 1.63 | 14.3 | 156 | 0 |
51 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.7) | Yes | Yes | 2.9 | 2.38 | 0.47 | 13.2 | 167 | 25.7 |
33 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (6.2) | Yes | No | 3.97 | 2.03 | 1.54 | 15.9 | 154 | 6.1 |
74 | F | LGL leukemia | PB | STAT3 c.1940A>T p.N647I (14.1)§ | ND | No | 8.11 | 3.91 | 3.37 | 8.9 | 472 | 0 |
CXCR4 NM_003467 c.702G>T p.K234N (16.3) | ||||||||||||
70 | M | LGL leukemia | PB | STAT3 c.1940A>T p.N647I (19.3) | I¶ | Yes | 9.52 | 2.19 | 6.56 | 11.7 | 160 | 0.7 |
91 | F | LGL leukemia | PB | STAT3 c.1981G>T p.D661Y (18.3) | Yes | No | 9.15 | 2.65 | 5.5 | 9.8 | 223 | 12.3 |
SETD2 c.1366C>T p.R456* (12.0) | ||||||||||||
TET2 c.1999_2000insTG p.H667fs* (15.7) | ||||||||||||
83 | M | LGL leukemia | PB | STAT3 c.1981G>T p.D661Y (22.7) | Yes | No | 2.8 | 0.45 | 1.79 | 12.1 | 145 | 13.4 |
SMC3 NM_005445 c.763C>T p.Q255* (10.0) | ||||||||||||
34 | F | LGL leukemia | PB | STAT3 c.1993T>A p.I665F (9.0) | Yes¶ | No | 3.09 | 1.19 | 1.68 | 12.8 | 158 | 13.2 |
29 | M | LGL leukemia | PB | STAT3 c.1993T>A p.I665F (9.7) | Yes | No | 4.23 | 1.27 | 2.42 | 14.5 | 153 | 18.5 |
69 | M | Reported MDS | BM | STAT3 c.1971_1971insAAG p.657insS (22.7) | Yes¶ | No | 2.48 | 1.17 | 1.02 | 8.0 | 349 | 24.7 |
75 | M | Reported MDS | PB | STAT3 c.1919A>T p.Y640F (18.9) | Yes | No | 2.02 | 0.28 | 1.18 | 14.4 | 220 | 8.9 |
75 | M | Reported MDS | PB | STAT3 c.1919A>T p.Y640F (6.9) | Yes¶ | Yes | 8.99 | 3.38 | 4.46 | 10.0 | 249 | 16.1 |
76 | F | Reported MDS | BM | STAT3 c.1919A>T p.Y640F (12.9) | Yes | Yes | 1.11 | 0.13 | 0.83 | 8.6 | 87 | 1.3 |
Age, y . | Sex . | NGS indication . | Specimen . | All somatic variants detected on NGS panel (VAF %) . | T-cell clonality* . | Splenomegaly . | WBCs, ×109/L . | Neutrophil count, ×109/L . | Lymphocyte count, ×109/L . | Hgb, g/dL . | Platelets, ×109/L . | Follow-up, mo† . |
---|---|---|---|---|---|---|---|---|---|---|---|---|
45 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (13.8) | Yes | No | 1.16 | 0.31 | 0.6 | 14.6 | 106 | 14.7 |
55 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (14.9)‡ | Yes | No | 3.27 | 0.97 | 1.81 | 14.0 | 212 | 4.2 |
51 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (19.4) | Yes | Yes | 4.6 | 1.15 | 3.04 | 11.4 | 187 | 13.0 |
69 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (2.3) | Yes | No | 3.23 | 1.36 | 1.54 | 9.5 | 51 | 24.5 |
STAT3 c.1165T>C p.T389A (10.7) | ||||||||||||
29 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (25.2) | Yes | Yes | 5.88 | 1.3 | 3.87 | 15.2 | 145 | 0 |
61 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (3.4) | Yes | Yes | 0.9 | 0.24 | 0.5 | 11.4 | 95 | 0 |
71 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (32.7) | Yes | No | 16.02 | 1.97 | 12.75 | 13.2 | 225 | 12.1 |
45 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (35.7) | Yes | No | 10.78 | 1.29 | 7.76 | 12.8 | 255 | 13.1 |
BRAF c.1781A>G p.D594G (4.7) | ||||||||||||
49 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (4.2) | Yes | No | 2.04 | 0.33 | 1 | 13.8 | 225 | 20.1 |
36 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.2) | Yes | No | 1.13 | 0.57 | 0.49 | 12.2 | 121 | 7.0 |
60 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.6) | Yes | No | 4.44 | 2.26 | 1.63 | 14.3 | 156 | 0 |
51 | F | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (5.7) | Yes | Yes | 2.9 | 2.38 | 0.47 | 13.2 | 167 | 25.7 |
33 | M | LGL leukemia | PB | STAT3 c.1919A>T p.Y640F (6.2) | Yes | No | 3.97 | 2.03 | 1.54 | 15.9 | 154 | 6.1 |
74 | F | LGL leukemia | PB | STAT3 c.1940A>T p.N647I (14.1)§ | ND | No | 8.11 | 3.91 | 3.37 | 8.9 | 472 | 0 |
CXCR4 NM_003467 c.702G>T p.K234N (16.3) | ||||||||||||
70 | M | LGL leukemia | PB | STAT3 c.1940A>T p.N647I (19.3) | I¶ | Yes | 9.52 | 2.19 | 6.56 | 11.7 | 160 | 0.7 |
91 | F | LGL leukemia | PB | STAT3 c.1981G>T p.D661Y (18.3) | Yes | No | 9.15 | 2.65 | 5.5 | 9.8 | 223 | 12.3 |
SETD2 c.1366C>T p.R456* (12.0) | ||||||||||||
TET2 c.1999_2000insTG p.H667fs* (15.7) | ||||||||||||
83 | M | LGL leukemia | PB | STAT3 c.1981G>T p.D661Y (22.7) | Yes | No | 2.8 | 0.45 | 1.79 | 12.1 | 145 | 13.4 |
SMC3 NM_005445 c.763C>T p.Q255* (10.0) | ||||||||||||
34 | F | LGL leukemia | PB | STAT3 c.1993T>A p.I665F (9.0) | Yes¶ | No | 3.09 | 1.19 | 1.68 | 12.8 | 158 | 13.2 |
29 | M | LGL leukemia | PB | STAT3 c.1993T>A p.I665F (9.7) | Yes | No | 4.23 | 1.27 | 2.42 | 14.5 | 153 | 18.5 |
69 | M | Reported MDS | BM | STAT3 c.1971_1971insAAG p.657insS (22.7) | Yes¶ | No | 2.48 | 1.17 | 1.02 | 8.0 | 349 | 24.7 |
75 | M | Reported MDS | PB | STAT3 c.1919A>T p.Y640F (18.9) | Yes | No | 2.02 | 0.28 | 1.18 | 14.4 | 220 | 8.9 |
75 | M | Reported MDS | PB | STAT3 c.1919A>T p.Y640F (6.9) | Yes¶ | Yes | 8.99 | 3.38 | 4.46 | 10.0 | 249 | 16.1 |
76 | F | Reported MDS | BM | STAT3 c.1919A>T p.Y640F (12.9) | Yes | Yes | 1.11 | 0.13 | 0.83 | 8.6 | 87 | 1.3 |
BM, bone marrow; F, female; Hgb, hemoglobin; M, male; ND, no data; I, indeterminate; NGS, next-generation sequencing; PB, peripheral blood; WBCs, white blood cells.
T-cell clonality determined by BIOMED-2 TCR-γ clonality assay.
All patients alive with disease at follow-up.
Concomitant rheumatoid arthritis.
Also germ line STAT3 NM_139276 c.832C>T p.R278C (VAF 48.2%).
NK cell–like immunophenotyped (sCD3-CD16+).