Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia

Abstract

Purpose of review: The past decade in LGL leukemia research has seen increased pairing of clinical data with molecular markers, shedding new insights on LGL leukemia pathogenesis and heterogeneity. This review summarizes the current standard of care of LGL leukemia, updates from clinical trials, and our congruent improved understanding of LGL pathogenesis.

Recent findings: Various clinical reports have identified associations between stem, bone marrow, and solid organ transplants and incidence of LGL leukemia. There is also a potential for underdiagnosis of LGL leukemia within the rheumatoid arthritis patient population, emphasizing our need for continued study. Preliminary results from the BNZ-1 clinical trial, which targets IL-15 along with IL-2 and IL-9 signaling pathways, show some evidence of clinical response. With advances in our understanding of LGL pathogenesis from both the bench and the clinic, exciting avenues for investigations lie ahead for LGL leukemia.

Keywords: Autoimmunity; BNZ-1; Large granular lymphocyte leukemia; Organ transplant; STAT3.

Conflict of interest statement

Disclosures: Thomas P. Loughran, Jr. is on the Scientific Advisory Board and has stock options for Keystone Nano and Bioniz Therapeutics. Thomas P. Loughran and David J. Feith have received honoraria from Kymera Therapeutics. There are no conflicts of interest with the work presented in this manuscript.

Figures

Figure 1:

Large granular lymphocytes are medium sized cells containing abundant granular cytoplasm, highlighted with arrows (A, 1000x). A bone marrow biopsy shows hypercellularity (B, 100x) and an interstitial non-paratrabecular lymphocytic infiltrate (C, 200x). The infiltrate is positive for CD3 (D, 100x) and CD8 (E, 100x). Many of the lymphoid cells are also positive for CD57 (F, 400x).