T-large granular lymphocytic leukemia

Abstract

T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway. Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.

Keywords: Diagnosis; T-cell large granular lymphocyte leukemia; Treatment.

Fig. 1

T-cell large granular lymphocyte (T-LGL) cells found in peripheral blood and bone marrow aspiration/ touch print. T-LGL cells found in peripheral blood (A and B, indicated with red arrows, ×1,000, Wright stain), bone marrow aspiration (C, indicated with red colored arrows, ×1,000, Wright stain), and touch print (D, indicated with red colored arrows, ×1,000, Wright stain) of a patient treated in the author’s hospital.

Fig. 2

Schematic diagram describing the pathogenesis of T-cell large granular lymphocytes (T-LGL). Activation and expansion of the oligoclonal cytotoxic lymphocyte population are caused by stimulation with an unknown antigen. While STAT3 is activated and/or mutated, chronic antigen stimulation leads to the expansion of one dominant (monoclonal) cytotoxic lymphocyte population. Persistent clonal expansion of monoclonal cytotoxic lymphocytes occurs by dysregulation of Fas/FasL-mediated cell death, which results in resistance to apoptosis.