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CHRONIC LYMPHOCYTIC LEUKEMIA

All that glitters is not LGL Leukemia

Leukemia volume 36, pages 2551–2557 (2022)Cite this article

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Abstract

LGL disorders are rare hematological neoplasias with remarkable phenotypic, genotypic and clinical heterogeneity. Despite these constraints, many achievements have been recently accomplished in understanding the aberrant pathways involved in the LGL leukemogenesis. In particular, compelling evidence implicates STAT signaling as a crucial player of the abnormal cell survival. As interest increases in mapping hematological malignancies by molecular genetics, the relevance of STAT gene mutations in LGL disorders has emerged thanks to their association with discrete clinical features. STAT3 and STAT5b mutations are recognized as the most common gain-of-function genetic lesions up to now identified in T-LGL leukemia (T-LGLL) and are actually regarded as the hallmark of this disorder, also contributing to further refine its subclassification. However, from a clinical perspective, the relationships between T-LGLL and other borderline and overlapping conditions, including reactive cell expansions, clonal hematopoiesis of indeterminate potential (CHIP) and unrelated clonopathies are not fully established, sometimes making the diagnosis of T cell malignancy challenging. In this review specifically focused on the topic of clonality of T-LGL disorders we will discuss the rationale of the appropriate steps to aid in distinguishing LGLL from its mimics, also attempting to provide new clues to stimulate further investigations designed to move this field forward.

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Fig. 1: Relationships between LGLL and other borderline and overlapping diseases.
Fig. 2: LGLL pathogenetic steps and disease’s aggressiveness.

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Acknowledgements

This work has been supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, IG-20216 to GS).

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  1. University of Padova, Padova, Italy

    Gianpietro Semenzato, Antonella Teramo, Giulia Calabretto, Vanessa Rebecca Gasparini & Renato Zambello

  2. Veneto Institute of Molecular Medicine, Padova, Italy

    Gianpietro Semenzato, Antonella Teramo, Giulia Calabretto, Vanessa Rebecca Gasparini & Renato Zambello

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  1. Gianpietro Semenzato
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GS contributed to the conceptualization of the Review, GS, AT, GC, VRG, RZ to the literature review and data collection. GS, AT, GC, RZ contributed to the figures. GS and RZ contributed to writing the original draft. GS, AT, GC, VRG, RZ contributed to review and edit subsequent drafts.

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Semenzato, G., Teramo, A., Calabretto, G. et al. All that glitters is not LGL Leukemia. Leukemia 36, 2551–2557 (2022). https://doi.org/10.1038/s41375-022-01695-x

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  • DOI: https://doi.org/10.1038/s41375-022-01695-x

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