Environmental, lifestyle, and familial/ethnic factors associated with myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by overproduction of mature functional blood cells and are often associated with an acquired genetic mutation of Janus Kinase 2V617F. The etiology of MPNs remains unknown. The aim of this article was to review and collate all known published data investigating environmental and lifestyle factors associated with MPNs. Medline, Embase, PubMed, Cochrane, and Web of Science were systematically searched using terms for MPNs and observational study designs to identify studies investigating the risk factors for MPNs published before March 2010. Of 9,156 articles identified, 19 met the selection criteria. Although the studies exhibited heterogeneity, in case definitions, study design, and risk factors investigated, several themes emerged. A strong association was found with Jewish descent, and with a family history of MPNs. Autoimmune conditions, specifically Crohn's disease, were more common in patients with MPNs. Certain occupational groups were significantly associated with MPNs including occupations with potential exposure to benzene and/or petroleum. Blood donation was associated with an increased risk of polycythemia vera specifically. The vast heterogeneity in studies identified as part of this review suggests that large scale systematic assessment of etiological factors associated with MPNs is warranted. (C) 2011 Wiley-Liss, Inc.

New prognostic markers, determined using gene expression analyses, reveal two distinct subtypes of chronic myelomonocytic leukaemia patients

Chronic myelomonocytic leukaemia (CMML) is a heterogeneous haematopoietic disorder characterized by myeloproliferative or myelodysplastic features. At present, the pathogenesis of this malignancy is not completely understood. In this study, we sought to analyse gene expression profiles of CMML in order to characterize new molecular outcome predictors. A learning set of 32 untreated CMML patients at diagnosis was available for TaqMan low-density array gene expression analysis. From 93 selected genes related to cancer and cell cycle, we built a five-gene prognostic index after multiplicity correction. Using this index, we characterized two categories of patients with distinct overall survival (94% vs. 19% for good and poor overall survival, respectively; P = 0.007) and we successfully validated its strength on an independent cohort of 21 CMML patients with Affymetrix gene expression data. We found no specific patterns of association with traditional prognostic stratification parameters in the learning cohort. However, the poor survival group strongly correlated with high-risk treated patients and transformation to acute myeloid leukaemia. We report here a new multigene prognostic index for CMML, independent of the gene expression measurement method, which could be used as a powerful tool to predict clinical outcome and help physicians to evaluate criteria for treatments.