Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia

Abstract

Large granular lymphocyte (LGL) syndrome includes a spectrum of clonal T cell and natural killer cell chronic lymphoproliferative disorders. These conditions are thought to arise from chronic antigenic stimulation, while the long-term survival of the abnormal LGLs appears to be sustained by resistance to apoptosis and/or impaired survival signaling. T-cell LGL (T-LGL) leukemia is the most common LGL disorder in the Western world. Despite its indolent course, the disease is often associated with neutropenia, the pathogenesis of which is multifactorial, comprising both humoral and cytotoxic mechanisms. This article addresses the pathogenesis of T-LGL leukemia and natural killer cell chronic lymphoproliferative disorder, as well as that of T-LGL leukemia-associated neutropenia. Furthermore, as symptomatic neutropenia represents an indication for initiating treatment, available therapeutic options are also discussed.

Keywords::

• apoptosis
• cytokine
• immunosuppression
• large granular lymphocyte leukemia
• natural killer cells
• neutropenia
• T cells

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.