Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia

Dipabarna Bhattacharya, Antonella Teramo, Vanessa Rebecca Gasparini, Jani Huuhtanen, Daehong Kim, Jason Theodoropoulos, Gianluca Schiavoni, Gregorio Barilà, Cristina Vicenzetto, Giulia Calabretto, Monica Facco, Toru Kawakami, Hideyuki Nakazawa, Brunangelo Falini, Enrico Tiacci, Fumihiro Ishida, Gianpietro Semenzato, Tiina Kelkka, Renato Zambello, Satu Mustjoki*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)
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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.

Original languageEnglish
Article number31
Pages (from-to)1-12
Number of pages12
JournalBlood Cancer Journal
Issue number2
Publication statusPublished - 24 Feb 2022
MoE publication typeA1 Journal article-refereed


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