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Objectives: Large granular lymphocyte (LGL) leukemia is a rare type of lymphoproliferative disease caused by clonal antigenic stimulation of T cells and natural killer (NK) cells. Methods: In this review, we focus on the current knowledge of the immunological dysfunctions associated with LGL leukemia and the associated disorders coexistent with this disease. Novel therapeutic options targeting known molecular mechanisms are also discussed. Results and Discussion: The pathogenesis of LGL leukemia involves the accumulation of gene mutations, dysregulated signaling pathways and immunological dysfunction. Mounting evidence indicated that dysregulated survival signaling pathways may be responsible for the immunological dysfunction in LGL leukemia including decreased numbers of neutrophils, dysregulated signal transduction of NK cells, abnormal B-cells, aberrant CD8+ T cells, as well as autoimmune and hematological abnormalities. Conclusion: A better understanding of the immune dysregulation triggered by LGL leukemia will be beneficial to explore the pathogenesis and potential therapeutic targets for this disease. [ABSTRACT FROM AUTHOR]

Objectives: Large granular lymphocyte (LGL) leukemia is a rare type of lymphoproliferative disease caused by clonal antigenic stimulation of T cells and natural killer (NK) cells. Methods: In this review, we focus on the current knowledge of the immunological dysfunctions associated with LGL leukemia and the associated disorders coexistent with this disease. Novel therapeutic options targeting known molecular mechanisms are also discussed. Results and Discussion: The pathogenesis of LGL leukemia involves the accumulation of gene mutations, dysregulated signaling pathways and immunological dysfunction. Mounting evidence indicated that dysregulated survival signaling pathways may be responsible for the immunological dysfunction in LGL leukemia including decreased numbers of neutrophils, dysregulated signal transduction of NK cells, abnormal B-cells, aberrant CD8+ T cells, as well as autoimmune and hematological abnormalities. Conclusion: A better understanding of the immune dysregulation triggered by LGL leukemia will be beneficial to explore the pathogenesis and potential therapeutic targets for this disease. [ABSTRACT FROM AUTHOR]

Presents several correspondence focused on leukemia. Efficacy of imatinib mesylate in conjunction with alpha-interferon; Imatnib mesylate-induced hepatotoxicity in chronic myeloid leukemia; Hepatitis C virus infection in patients with B-cell lymphoproliferative disorders; Lack of p53 expression in human myeloid leukemia.

Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated neutropenia represents the clinical hallmark of the disease, being present in up to 80% of cases. New advances were made in the biological characterization of neutropenia in these patients, in particular STAT3 mutations and a discrete immunophenotype are now recognized as relevant features. Nevertheless, the etiology of LGLL-related neutropenia is not completely elucidated and several mechanisms, including humoral abnormalities, bone marrow infiltration/substitution and cell-mediated cytotoxicity might cooperate to its pathogenesis. As a consequence of the multifactorial nature of LGLL-related neutropenia, a targeted therapeutic approach for neutropenic patients has not been developed yet; moreover, specific guidelines based on prospective trials are still lacking, thus making the treatment of this disorder a complex and challenging task. Immunosuppressive therapy represents the current, although poorly effective, therapeutic strategy. The recent identification of a STAT3-mediated miR-146b down-regulation in neutropenic T-LGLL patients emphasized the pathogenetic role of STAT3 activation in neutropenia development. Accordingly, JAK/STAT3 axis inhibition and miR-146b restoration might represent tempting strategies and should be prospectively evaluated for the treatment of neutropenic LGLL patients. [ABSTRACT FROM AUTHOR]