Determining the underlying cause of persistent eosinophilia is important for effective clinical management but remains a diagnostic challenge in many cases. We identified STAT5B N642H, an established oncogenic mutation, in 27/1715 (1.6%) cases referred for investigation of eosinophilia. Of the 27 mutated cases, a working diagnosis of hypereosinophilic syndrome (HES; n = 7) or a myeloid neoplasm with eosinophilia (n = 20) had been made prior to the detection of STAT5B N642H. Myeloid panel analysis identified a median of 2 additional mutated genes (range 0–4) with 4 cases having STAT5B N642H as a sole abnormality. STAT5B N642H was absent in cultured T cells of 4/4 positive cases. Individuals with SF3B1 mutations (9/27; 33%) or STAT5B N642H as a sole abnormality had a markedly better overall survival compared to cases with other additional mutations (median 65 months vs. 14 months; hazard ratio = 8.1; P < 0.001). The overall survival of STAT5B-mutated HES cases was only 30 months, suggesting that these cases should be reclassified as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS). The finding of STAT5B N642H as a recurrent mutation in myeloid neoplasia with eosinophilia provides a new diagnostic and prognostic marker as well as a potential target for therapy.
Genetic factors are known to be important in the development of Hodgkin lymphoma (HL). Interleukin-10 (IL-10) secretion by both malignant and reactive cells is thought to be important in the pathogenesis of HL especially Epstein-Barr virus (EBV) positive cases. Polymorphisms of the IL-10 gene have been reported to be associated with susceptibility to EBV infection. The cytotoxic response to EBV is determined by a Th1 biased immune response which is characterised by interferon gamma (IFNgamma) secretion. We therefore investigated polymorphisms in the IL-10 (-1082 G/A and -592 C/A) and IFNgamma (intron 1 CA repeat) genes as predisposing factors in the development 147 cases of HL. A difference of borderline statistical significance was demonstrated for the IFNgamma gene polymorphism but significance was lost when analysis was restricted to the common genotypes. No significant differences in the distributions of genotypes were found for the IL-10 gene polymorphisms. IL-10 and IFNgamma levels were also measured on 26 patients with HL. No statistically significant differences were detected when the results were analysed by genotype. We found little evidence IL-10 and IFNgamma genotypes predispose to the development of HL or influence the inflammatory host response.
Pyoderma gangrenosum (PG) may be associated with inflammatory disorders and haematological conditions such as monoclonal gammopathy of uncertain significance (MGUS). We report the case of a 53-year old man who had PG and MGUS. After treatment with infliximab for the PG, he developed myeloma. The course of events in this case suggests that infliximab facilitated the progression from MGUS to myeloma.
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