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Abstract: The term myelodysplastic syndromes (MDS) include a diverse group of diseases in which the bone marrow production of blood cells is disrupted. In spite of the wealth of information on therapeutic options, little is known about the epidemiology of MDS, including population variations and risk factors. A narrative review of published literature and meta-analyses were conducted, identifying and summarizing key reports that describe the association between smoking, alcohol and MDS. There were 10 case–control studies that looked at the association between smoking and MDS, for a total of 1839 cases and 2831 controls. The meta-estimate for the association between ever smoking and MDS was 1.45 (95% CI: 1.21–1.74), with heterogeneity among studies (p =0.05), but no evidence of publication bias. The relationship between alcohol consumption and MDS has been examined in five studies, including 745 cases and 1642 controls. The overall association was 1.31 (95% CI: 0.79–2.18), with significant heterogeneity (p =0.003) and no evidence of publication bias. This re-analysis of published data strongly suggests that smoking is significantly associated with MDS, while alcohol does not seem to play a major role in MDS etiology. Large epidemiological studies incorporating biomarkers of exposure, along with pooled analysis are needed to better address the contribution of lifestyle factors to the development of MDS. [Copyright &y& Elsevier]

Abstract: We explored the potential involvement of FoxO3a activation in erythroid and granulocytic differentiation for Ph+ cells of chronic myeloid leukemia blast crisis (CML BC). We demonstrate that FoxO3a activation in CML blast crisis (BC) cells by overexpressing FoxO3a leads to the maturation of CML BC cells. Hemoglobin production significantly increased upon FoxO3a activation in CML BC cells. FoxO3a activation upregulated erythroid surface protein (glycophorin A, GPA), but did not significantly modulate granulocytic markers (CD11b). Additionally, FoxO3a activation reduced the mRNA and protein expression of Tal1. Similar results were observed in cells that were given nilotinib. Our results indicate that FoxO3a activation may promote erythroid differentiation of BC cells via down-regulating Tal1 expression. [Copyright &y& Elsevier]