Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2022-02-24
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en
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12
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Blood Cancer Journal, Volume 12, issue 2, pp. 1-12
Abstract
CD4+ T-cell large granular lymphocyte leukemia (T-LGLL) is a rare subtype of T-LGLL with unknown etiology. In this study, we molecularly characterized a cohort of patients (n = 35) by studying their T-cell receptor (TCR) repertoire and the presence of somatic STAT5B mutations. In addition to the previously described gain-of-function mutations (N642H, Y665F, Q706L, S715F), we discovered six novel STAT5B mutations (Q220H, E433K, T628S, P658R, P702A, and V712E). Multiple STAT5B mutations were present in 22% (5/23) of STAT5B mutated CD4+ T-LGLL cases, either coexisting in one clone or in distinct clones. Patients with STAT5B mutations had increased lymphocyte and LGL counts when compared to STAT5B wild-type patients. TCRβ sequencing showed that, in addition to large LGL expansions, non-leukemic T cell repertoires were more clonal in CD4+ T-LGLL compared to healthy. Interestingly, 25% (15/59) of CD4+ T-LGLL clonotypes were found, albeit in much lower frequencies, in the non-leukemic CD4+ T cell repertoires of the CD4+ T-LGLL patients. Additionally, we further confirmed the previously reported clonal dominance of TRBV6-expressing clones in CD4+ T-LGLL. In conclusion, CD4+ T-LGLL patients have a typical TCR and mutation profile suggestive of aberrant antigen response underlying the disease.Description
| openaire: EC/H2020/647355/EU//M-Imm
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Bhattacharya, D, Teramo, A, Gasparini, V R, Huuhtanen, J, Kim, D, Theodoropoulos, J, Schiavoni, G, Barilà, G, Vicenzetto, C, Calabretto, G, Facco, M, Kawakami, T, Nakazawa, H, Falini, B, Tiacci, E, Ishida, F, Semenzato, G, Kelkka, T, Zambello, R & Mustjoki, S 2022, ' Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia ', Blood Cancer Journal, vol. 12, no. 2, 31, pp. 1-12 . https://doi.org/10.1038/s41408-022-00630-8