[Large granular lymphocyte proliferations. Clinical and pathogenic aspects]

Area of Science:

• Hematology
• Immunology
• Oncology

Background:

• Large granular lymphocyte (LGL) leukemia is a clonal disorder of T-cells or NK-cells, often presenting with neutropenia and splenomegaly.
• Diagnosis relies on identifying excess LGLs and assessing T-cell receptor clonality via immunophenotypic and molecular studies.
• Associated autoimmune conditions are common, and potential roles of viral agents, cytokines, and defective apoptosis are under investigation.

Purpose of the Study:

• To review the clinical course, biological features, and pathogenesis of large granular lymphocyte (LGL) leukemia.
• To discuss current knowledge regarding diagnosis, associated conditions, and potential etiological factors.
• To highlight the need for further research into the epidemiology, prognosis, and therapeutics of LGL leukemia.

Main Methods:

• Review of existing literature on large granular lymphocyte (LGL) leukemia.
• Analysis of diagnostic criteria, including immunophenotypic and molecular studies for T-cell receptor clonality.
• Discussion of pathogenetic hypotheses, including viral infections, cytokine involvement, and apoptosis defects.

Main Results:

• LGL leukemia can originate from either T-cell (CD3+, CD57+) or NK-cell (CD3-, CD56+) lineages.
• Association with autoimmune diseases is a significant feature of chronic LGL proliferation.
• Current understanding of LGL leukemia's epidemiology, prognosis, and optimal therapeutics remains limited.

Conclusions:

• The pathogenesis, epidemiology, prognosis, and therapeutics of LGL leukemia require further investigation.
• A French registry for LGL expansions is proposed to facilitate comprehensive research into these aspects.
• Current treatment for symptomatic LGL proliferations involves immunosuppressive agents like methotrexate and cyclophosphamide.