Table 1.
Distribution of SH2 domain STAT3 and STAT5B gene mutations in LGLL patients and clonal T/NK-cell populations investigated in this study, grouped per disease category.
| Panel A: Distribution of STAT3 and STAT5B Gene Mutations in the LGLL Patients and Clonal T/NK-Cell Populations | ||||||||||||||
| LGL Cell Lineage | Mutated Gene | |||||||||||||
| STAT3 Gene Mutations | STAT5B Gene Mutations | Total | ||||||||||||
| Exon 20 | Exon 21 | Exon 16 | ||||||||||||
|
T-LGLL Cases 22/66 (33%) Cell pop. 25/78 (32%) |
TCD8+ | N. Cases | 1/32 (3%) | 11/33 (33%) | 0/33 (0%) | 12/33 (36%) | ||||||||
| N. cell pop. | 3/43 (7%) | 12/44 (27%) | 0/44 (0%) | 15/44 (34%) | ||||||||||
| TCD4+ | N. Cases | 0/14 (0%) | 0/14 (0%) | 1/14 (7%) | 1/14 (7%) | |||||||||
| N. cell pop. | 0/15 (0%) | 0/15 (0%) | 1/15 (7%) | 1/15 (7%) | ||||||||||
| Tαβ+DP | N. Cases (=N. cell pop.) |
0/1 (0%) | 1/1 (100%) | NA | 1/1 (100%) | |||||||||
| Tαβ+DN | N. Cases (=N. cell pop.) |
0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) | |||||||||
| Tγδ+ | N. Cases (=N. cell pop.) |
2/15 (13%) | 5/16 (31%) | 0/15 (0%) | 7/16 (44%) | |||||||||
|
CLPD-NK 6/16 (38%) |
CD56−/+lo | N. Cases (=N. cell pop.) |
0/6 (0%) | 4/7 (57%) | 0/6 (0%) | 4/7 (57%) | ||||||||
| CD56+ | N. Cases (=N. cell pop.) |
1/7 (14%) | 1/7 (14%) | 0/7 (0%) | 2/7 (29%) | |||||||||
| CD56++ | N. Cases (=N. cell pop.) |
0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | |||||||||
| Total | N. Cases | 4/79 (5%) | 23/82 (28%) | 1/79 (1%) | 28/82 (34%) | |||||||||
| N. cell pop. | 6/91 (7%) | 24/94 (26%) | 1/91 (1%) | 31/94 (33%) | ||||||||||
| Panel B: Specific STAT3/5B Gene Mutations Identified in Purified Clonal T/NK-cell LGL Populations (n = 31) from 28 T/NK-LGLL Patients | ||||||||||||||
| Disease Clonal Cell Population Category | Mutated Gene | |||||||||||||
| STAT3 Mutations | STAT5B Mut | |||||||||||||
| Exon 20 | Exon 21 | Exon 16 | ||||||||||||
|
S614R
(n = 2) |
G618R
(n = 4) |
Y640F
(n = 15) |
N647I
(n = 1) |
G656ins
(n = 1) |
Y657dup
(n = 2) |
K658F *
(n = 1) |
D661V
(n = 2) |
D661Y
(n = 2) |
Y665F
(n = 1) |
|||||
| T-LGLL | TCD8+ | 3 (20%) | 9 (60%) | 1 (7%) | 1 (7%) | 1 (7%) | ||||||||
| TCD4+ | 1 (100%) | |||||||||||||
| Tαβ+DP | 1 (100%) | |||||||||||||
| Tαβ+DN | 1 (100%) | |||||||||||||
| Tγδ+ | 2 (29%) | 3 (43%) | 1 (14%) | 1 (14%) | ||||||||||
| CLPD-NK | CD56−/+lo | 1 (25%) | 1 (25%) | 2 (50%) | ||||||||||
| CD56+ | 1 (50%) | 1 (50%) | ||||||||||||
Results expressed as number (percentage) of mutated LGL cases or cell populations analyzed (in italics) per disease type. Panel B: Empty cell means 0 cases. * Gene mutation not previously described. A total of 3/28 patients showed two different clonal LGL populations with distinct STAT3 gene mutations: (i) 1/3 cases had the Y640F and Y657dup gene mutations in two different clonal populations of TCD8+ cells; (ii) 1/3 cases showed the S614R and G618R STAT3 gene mutations in one clonal Tγδ+ population and one clonal TCD8+-cell population, respectively; (iii) 1/3 cases displayed the Y640F and G618R mutations in one clonal CD56−/+lo NK-cell population and one clonal TCD8+-cell population, respectively. Abbreviations (alphabetical order): CLPD-NK, chronic lymphoproliferative disorders of NK cells; dup, duplication; LGL, large granular lymphocyte; Mut, mutation; N., number; NA, not analyzed; Pop., populations; SH2, Src homology 2; T-LGLL, leukemia of T large granular lymphocytes.