Immunogenetic factors determining the evolution of T-cell large granular lymphocyte leukaemia and associated cytopenias

Authors


Jaroslaw Maciejewski, MD, PhD, Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center R-40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA.
E-mail: maciejj@ccf.org

Summary

T-cell large granular lymphocyte leukaemia (T-LGL) is a chronic clonal proliferation of cytotoxic T lymphocytes (CTL). T-LGL presents with cytopenias, often accompanied by autoimmune diseases, suggesting clonal transformation arising from an initially polyclonal immune response. Various immunogenetic predisposition factors, previously described for both immune-mediated bone marrow failure and autoimmune conditions, may promote T-LGL evolution and/or development of cytopenias. The association of T-LGL was analysed with a number of immunogenetic factors in 66 patients, including human leucocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) genotype, KIR/KIR-L mismatch, CTLA-4 (+49 A/G),CD16158V/F, CD45 polymorphisms, cytokine single nucleotide polymorphisms including: TNF-α (−308G/A), TGF-β1 (codons 10 C/T, 25 G/C), IL-10 (−1082 G/A), IL-6 (−174 C/G), and IFN-γ(+874 T/A). A statistically significant increase in A/A genotype for TNF-α−308, IL-10–1082, andCTLA-4 +49 was observed in T-LGL patients compared with control, suggesting that the G allele serves a protective role in each case. No association was found between specific KIR/HLA profile and disease. KIR/KIR-L analysis revealed significant mismatches between KIR3DL2 and KIR2DS1 and their ligands HLA-A3/11 and HLA-C group 2 (P = 0·03 and 0·01 respectively); the biological relevance of this finding is questionable. The significance of additional genetic polymorphisms and their clinical correlation to evolution of T-LGL requires future analysis.

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