CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V beta genes

Area of Science:

• Hematology
• Immunology
• Oncology

Background:

• CD3+ large granular lymphocyte (LGL) leukemia is a clonal T cell proliferation of unknown cause.
• Rheumatoid arthritis (RA) frequently co-occurs with LGL leukemia, and clonally expanded T cells are implicated in RA pathogenesis.

Purpose of the Study:

• To investigate the etiology of CD3+ LGL leukemia by identifying T-cell receptor (TCR) beta-chain variable (V), joining (J), and diversity (D) region genes used by leukemic cells.
• To explore potential links between TCR gene usage in LGL leukemia and the frequent co-occurrence with rheumatoid arthritis.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from 12 LGL leukemia patients were analyzed.
• TCR beta-chain V gene expression was assessed using polymerase chain reaction (PCR) with 22 V beta primers.
• Clonality was confirmed by sequencing subcloned V-D-J region DNA fragments.

Main Results:

• A dominant V beta gene product was identified in all patients, indicating clonal expansion.
• The distribution pattern of expressed V beta and J beta genes mirrored their representation in normal peripheral blood.
• While no specific VDJ usage pattern was found for LGL leukemia with RA, V beta-6 usage was noted in LGL clones exclusively in the context of RA.

Conclusions:

• Leukemic CD3+ LGL cells appear to undergo clonal transformation in a random manner concerning their TCR beta chain gene usage.
• The specific association of V beta-6 with LGL clones in RA patients warrants further investigation into potential shared pathogenetic mechanisms.