Lymphomas arising from NK or gd-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n ¼ 51), gd-T-cell lymphomas (n ¼ 43) and their cell lines (n ¼ 9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of gd-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.

BackgroundThe subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China.MethodsLymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification.ResultsFrom January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin.ConclusionsThe lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial. METHODS: A phase 2 study was conducted of ''sandwich'' protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L-asparaginase, vincristine, and prednisone), followed by further ''consolidation'' cycles. Patients aged 18 years and older who had previously untreated ENKTL and localized lesions in the upper aerodigestive tract were enrolled. The primary endpoints were objective response rate and complete remission rate. The secondary endpoints were 2-year overall survival, 2-year progression-free survival, and toxicity. This study is registered with www.Chictr.org, number ChicTR-TNC-00000394, and is ongoing for long-term follow-up. RESULTS: Twenty-six patients completed total therapy, which resulted in 88.5% response that included 21 patients (80.8%) with complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%) of 26 patients progressed during therapy. With a median follow-up of 27 months (range, 4-35 months), the 2-year overall survival was 88.5%, and the 2-year progression-free survival was 80.6%. Patients with CR had better prognosis than patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia. No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: The research showed that the ''sandwich'' protocol of LVP combined with RT was a safe and effective treatment for localized nasal natural killer/T-cell lymphoma, and the results warrant further investigation into this protocol. Cancer 2012;118:3294-

To estimate the distribution of lymphoid neoplasms in China, we conducted a comprehensive analysis, based on subtype, age, sex, and lesion, of primary and resected biopsy specimens of 4,638 lymphoid neoplasms diagnosed from 2004 to 2008 at 5 large hospitals. Of the 4,638 patients, mature B-cell neoplasms accounted for 64.3% of all lymphoid neoplasms, mature T/NK-cell neoplasms for 23.3%, and Hodgkin lymphoma for 8.6%. The most common subtype was diffuse large B-cell lymphoma (36.2%), followed by extranodal NK/T-cell lymphoma, nasal type (11.0%), classic Hodgkin lymphoma (8.4%), extranodal marginal zone B-cell lymphoma (7.7%), plasmacytic neoplasm (5.0%), and peripheral T-cell lymphoma, not otherwise specified (3.9%). For most lymphoid neoplasm subtypes, male subjects showed higher rates than female subjects. In summary, our study showed that the epidemiologic features of lymphoid neoplasms in China are distinct from those in Western countries and similar in many ways to those in other countries of the Far East.

BackgroundSystemic immune-inflammation index (SII) is a novel inflammatory marker, and inflammation has been reported to be related with renal damage. We aimed to investigate the possible relationship between SII and albuminuria.MethodsThe present cross-sectional study was conducted among adults with complete data about SII and urinary albumin-to-creatinine ratio (ACR) in 2005–2018 National Health and Nutrition Examination Survey (NHANES). SII was calculated as the platelet count × neutrophil count/lymphocyte count. Albuminuria was defined as ACR >30mg/g. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between SII and albuminuria.ResultsA total of 36,463 individuals were included in our analysis; 9.56% participants were categorized as having albuminuria overall and increased with the higher SII tertiles (tertile 1, 7.83%; tertile 2, 8.49%; tertile 3, 12.13%; p for trend <0.0001). Multivariable logistic regression showed that a higher SII level was associated with increased likelihood of albuminuria independently (OR = 1.31; 95% CI, 1.17–1.48, p<0.0001) after full adjustment. Subgroup analysis and interaction test showed that there was no significant dependence of gender, age, body mass index, hypertension, diabetes, non‐alcoholic fatty liver disease, and estimated glomerular filtration rate (eGFR) on this positive association (all p for interaction >0.05).ConclusionsSII was positively associated with increased urinary albumin excretion in US adults. Further large-scale prospective studies are still needed to analyze the role of SII in albuminuria.