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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.

Summary

With advances in our understanding of LGL pathogenesis from both the bench and the clinic, exciting avenues for investigations lie ahead for LGL leukemia.

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Fig. 1

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Acknowledgments

We thank Bryna Shemo and Rachel Stidham for LGL Leukemia Registry support. We wish to extend a special thanks to the LGL Leukemia Registry patients for their enthusiastic support and interest in our research.

Funding

LGL leukemia research in the Loughran lab is supported by the National Cancer Institute of the National Institutes of Health under award number R01CA178393 and P30CA044579 (to TPL) and the NIH Cancer Research Training in Molecular Biology Award T32CA009109 (to KBM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the Bess Family Charitable Fund, the LGL Leukemia Foundation, and a generous anonymous donor.

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Correspondence to Thomas P. Loughran Jr..

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Conflict of Interest

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.

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Cheon, H., Dziewulska, K.H., Moosic, K.B. et al. Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia. Curr Hematol Malig Rep (2020). https://doi.org/10.1007/s11899-020-00565-6

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Keywords

  • Large granular lymphocyte leukemia
  • STAT3
  • Autoimmunity
  • Organ transplant
  • BNZ-1