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STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features.Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8±) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France).Our results indicate that i) CD8+ T-LGL leukemia patients with CD16+/CD56- immunophenotype identify a subset of patients characterized by the presence of STAT3 mutations and neutropenia, ii) CD4+/CD8± T-LGL leukemia are devoid of STAT3 mutations but characterized by STAT5b mutations, and iii) a correlation exists between STAT3 activation and presence of Fas ligand, this molecule resulting highly expressed in CD8+/CD16+/CD56- patients. Experiments with stimulation and inhibition of STAT3 phosphorylation confirmed this relationship. In conclusion, our data show that T-LGL leukemia with specific molecular and phenotypic patterns is associated with discrete clinical features contributing to get insights into molecular bases accounting for the development of Fas ligand-mediated neutropenia.

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The translocation t(8;9)(p22;p24) results in the production of a chimeric PCM1 ‐ JAK2 fusion protein leading to the constitutive activation of the Janus Kinase 2 that renders this disease potentially sensitive to ruxolitinib. Here, we report an interesting case of PCM1 ‐ JAK2 myeloproliferative neoplasm evolving in myeloid sarcoma and B precursor ALL.

Large granular lymphocyte (LGL) leukemia belongs to the chronic mature lymphoproliferative disorders of the T/natural killer (NK) lineage. 1 T-LGL leukemia, which accounts for 85% of cases, and chronic lymphoproliferative disorder of NK cells (CLPD-NK), are indolent diseases with the same clinical and biological features. 1 Overall 10-year survival of patients with T-and NK-LGL leukemia is about 70%, and the estimated frequency is 2% to 5% of chronic lymphoproliferative diseases in North America and 5% to 6% in Asia. 2 Clinical presentations are related mainly to recurrent bacterial infections associated with neutropenia and/or anemia. Associated diseases, such as autoimmune cytopenia, B-cell lymphoma, myelodysplastic syndrome, vasculitis, and autoimmune disease, are commonly observed. Sporadic cases of pulmonary arterial hypertension (PAH) have been reported 3-7 in patients with LGL leukemia. Whether or not this association is fortuitous remains unknown, and its incidence seems to be < 0.5%. In group 5 of the pulmonary hypertension (PH) classification, hematologic disorders are discussed. 8 However, lymphoproliferative disorders are not mentioned. This article reports on a descriptive cohort of nine patients presenting with precapillary pulmonary hypertension and LGL leukemia. Methods This international cohort included patients compiled retrospectively from the French, Italian, and American national LGL registries. All patients fulfilled the usual LGL leukemia diagnostic criteria, 9 with circulating LGLs exceeding 0.5 Â 10 9 /L. Criteria for T-LGL leukemia included typical expression of T-LGL surface markers on peripheral blood (CD3 þ CD8 þ CD57 þ and/or CD16 þ) associated with a T-cell receptor g gene clonal rearrangement or clonal V b expression on flow cytometry. Criteria for NK-LGL leukemia included expression of NK-LGL markers (CD3-CD8 þ /CD16 þ and/or CD56). The hematologic complete response and partial response criteria were considered after 4 months of treatment according to those previously published. 9