STAT3 mutations are present in aggressive B-cell lymphomas including a subset of diffuse large B-cell lymphomas with CD30 expression

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells

“…Although STAT3 or STAT5B mutations have been reported in malignancies such as B-cell lymphomas 23 , angioimmunoblastic T-cell lymphoma 24 , CD30 þ T-cell lymphoma 25 , the indolent LGLL diseases [26][27][28] and recently in T-cell prolymphocytic leukaemia 29 , which also included functional characterization of STAT5 mutations, our study describes prevalent activating STAT5B and STAT3 mutations in aggressive lymphomas of NK and gd-T cell of origin. Importantly, we provided strong in vitro functional data that support an oncogenic role of these mutants as well as mechanistic insight into how the N642H mutant acquires enhanced functional activities.…”

Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell–derived lymphomas

“…We also identified a novel K18N mutation (variant frequency [VF] [5.5%; 7.4%; 10%]) in 3 AITL patients ( Figure 3A; Table 1). [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Both mutations occur in the highly conserved GTP binding site of RHOA. We tested Myc-tagged (C) SRE (serum-responsive element) luciferase reporter assay monitoring the activity of RHOA K18N mutant, compared with WT, G14V, or G17V mutants, previously characterized as activating and dominant-negative, respectively.…”

The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia

“…As an extreme example, two patients harbored four different STAT3 mutations (Figure 1). Patients with multiple STAT3 mutations could be divided into two different groups based on the allelic status derived from the amplicon data: (i) patients harboring two single nucleotide variants in the same STAT3 allele, resulting in one or two amino acid changes (n=4, Figure 1, patients 1-4), and (ii) patients displaying multiple STAT3 mutations in different alleles and lymphocyte clones (n=14, Figure 1, patients [5][6][7][8][9][10][11][12][13][14][15][16][17][18] …”

“…8,9,14 Expression of mutated STAT3 in mouse bone marrow led to the development of myeloproliferative neoplasm, and recently similar STAT3 and STAT5b mutations have also been discovered in other hematologic malignancies. 12,[15][16][17][18][19] In this project we aimed to analyze the frequency of STAT3 mutations and the clonal architecture of expanded lymphocytes using both STAT3 and TCR beta (TCRB) chain deep sequencing methods in a unique cohort of 213 patients with LGL leukemia. In addition, the effect of immunosuppressive treatment on the mutated clones was studied in follow-up samples obtained during therapy to assess if quantitative STAT3 mutation analysis could be used to monitor therapy response.…”