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Prevalence of STAT3 mutations in patients with rheumatoid arthritis-associated T-cell large granular lymphocytic leukaemia and Felty syndrome
V. Gorodetskiy1, Y. Sidorova2, B. Biderman3, N. Ryzhikova4, V. Vasilyev5, A. Sudarikov6
- V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia. gorodetskiyblood@mail.ru
- Laboratory of Molecular Haematology, National Medical Research Center for Haematology, Moscow, Russia.
- Laboratory of Molecular Haematology, National Medical Research Center for Haematology, Moscow, Russia.
- Laboratory of Molecular Haematology, National Medical Research Center for Haematology, Moscow, Russia.
- Joint and Heart Treatment Center, Moscow, Russia.
- Laboratory of Molecular Haematology, National Medical Research Center for Haematology, Moscow, Russia.
CER16526
2024 Vol.42, N°1
PI 0048, PF 0055
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PMID: 37497725 [PubMed]
Received: 19/01/2023
Accepted : 15/06/2023
In Press: 24/07/2023
Published: 24/01/2024
Abstract
OBJECTIVES:
Neutropenia is a key presentation of Felty syndrome (FS) and rheumatoid arthritis (RA)-associated T-cell large granular lymphocytic (T-LGL) leukaemia. Clonal rearrangement of T-cell receptor (TCR) gene supports the diagnosis of T-LGL leukaemia but not FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) gene are highly specific for T-LGL leukaemia, but their prevalence in FS remains poorly clarified.
METHODS:
The study included 100 patients with RA and unexplained neutropenia. TCR rearrangements were examined in blood (100 cases), bone marrow (47 cases), and spleen (12 cases) using the BIOMED-2 protocol. Patients were stratified into RA-associated T-LGL leukaemia cohort if a clonal TCR rearrangement was identified in any of the tested patient samples, and into FS cohort in other cases. Mutations in the STAT3 were examined using next-generation sequencing (NGS) technology in blood (100 cases), bone marrow (37 cases), and spleen (7 cases).
RESULTS:
STAT3 mutations were identified in 71% (49/69) patients with RA-associated T-LGL leukaemia and in 10% (3/31) patients with FS (p=4.7×10-8). Three samples from the RA-associated T-LGL leukaemia cohort and 5 samples from the FS cohort had STAT3 mutations in the absence of clonal TCR rearrangement.
CONCLUSIONS:
The results suggest that STAT3 mutations are significantly less common in FS than in RA-associated T-LGL leukaemia. Moreover, NGS can detect clones undetectable by fragment analysis. We speculate that in patients with RA and neutropenia, the detection of STAT3 mutations can point to T-LGL leukaemia even in the absence of clonal TCR rearrangement.