Leukemias of T-cell large granular lymphocytes and natural killers

Abstract

Leukemias of large granular lymphocytes (LGL) include a heterogeneous group of rare lymphoid malignancies derived from T cells (T-LGL) and natural killers (NK-LGL) T-LGL leukemia arises from long-term antigen stimulation and the survival of LGL cells is associated with constitutive activation of anti-apoptotic intracellular pathways JAK/STAT, RAS/RAF/MEK/ERK, sphingolipids and extracellular FAS/FASL. The clinical course may be indolent or aggressive where majority of patients present clinical symptoms such as cytopenia, organomegaly and underlying autoimmune diseases; particularly rheumatoid arthritis. Diagnosing LGL leukemia is based on flow cytometry and T-cell receptor gene rearrangement. Most patients also require treatment for severe neutropenia complicated infections. T-LGL leukemia therapy is mainly immunosuppressive; the drug of choice in the first line is methotrexate or cyclophosphamide but there are no established standards for treating LGL leukemia. Both chronic T/NK-LGL leukemias exhibit an indolent clinical course with a favorable prognosis, whereas aggressive T/NK-LGL leukemias are progressive diseases with poor prognosis.