Anti-Inflammatory Response to Anti-Folate and Vitamin D Analog Combination in Large Granular Lymphocyte Leukemia

Large granular lymphocyte (LGL) leukemia is a rare chronic hematological disorder characterized by clonal expansion of circulating cytotoxic T or natural killer (NK) cells. The disease is associated with a number of comorbidities including neutropenia, anemia, and autoimmune diseases. There is no standard of care or curative therapy for LGL leukemia. Instead, it is treated when symptoms arise with a variety of immunosuppressive therapies, chief among them, the anti-folate, methotrexate (MTX). However, a significant proportion of patients remain refractory to treatment, and little characterization has been done regarding MTX's mechanism in vitro. Thus, there is a need to identify new therapeutic approaches such as stronger anti-folates or combination of MTX with existing therapies.