The complex relationship between large granular lymphocyte leukemia and rheumatic disease

ABSTRACT

Introduction

Large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or NK lymphocytes. Neutropenia-related infections represent the main clinical manifestation. Even if the disease follows an indolent course, most patients will ultimately need treatment in their lifetime. Interestingly, LGL leukemia is characterized by a high frequency of autoimmune disorders with rheumatoid arthritis being the most frequent.

Areas covered

This review covers the pathophysiology, clinic-biological features and the advances made in the treatment of LGL leukemia. A special focus will be made on the similarities in the pathophysiology of LGL leukemia and the frequently associated rheumatic disorders.

Expert opinion

Recent advances in the phenotypic and molecular characterization of LGL clones have uncovered the key role of JAK-STAT signaling in the pathophysiology linking leukemic cells expansion and autoimmunity. The description of the molecular landscape of T- and NK-LGL leukemia and the improved understanding of the associated rheumatic disorders open the way to the development of new targeted therapies effective on both conditions.

KEYWORDS:

• Autoimmune disorders
• interleukin-15
• large granular lymphocytic leukemia
• NKG2D
• rheumatoid arthritis
• STAT3

Article highlights

• Large granular lymphocytic leukemia (LGL) is a rare chronic lymphoproliferative disorder at the interface between cancers and autoimmune diseases.

• Rheumatic disorders, especially rheumatoid arthritis can occur before, simultaneously or after the diagnosis of LGL leukemia.

• Recent advances have uncovered the significant role of STAT3 gain of function mutations in the pathophysiology linking LGL leukemia and auto-immunity.

• Improvement in the understanding of the disease opens the way to new therapeutical developments targeting the JAK-STAT pathway, inflammatory cytokines signaling and epigenetic modifications.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.