BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

Occurrence of phenotypic abnormalities in CD34þ hematopoietic progenitor and precursor cells (HPC) and their major B-cell and nonlymphoid compartments has been frequently reported in myelodysplastic syndromes (MDS). Here, we analyze for the first time the numerical and phenotypic abnormalities of different maturation-associated subsets of bone marrow (BM) CD34þ HPC from 50 newly diagnosed MDS patients in comparison to normal/reactive BM (n ¼ 29). Our results confirm the existence of heterogeneously altered phenotypes among CD34 þ HPC from MDS and indicate that such variability depends both on the relative distribution of the different subsets of CD34 þ HPC committed into the different myeloid and B-lymphoid compartments, and their immunophenotype (for example, higher reactivity for CD117 and CD13 and lower expression of CyMPO, CD64 and CD65 on CD34 þ immature and neutrophil precursors), a clear association existing between the accumulation of CD34 þ HPC and that of immature CD34 þ HPC. Interestingly, expansion of erythroidand neutrophil-lineage CD34 þ cells is detected in low-grade MDS at the expense of CD34 þ plasmacytoid dendritic cell and B-cell precursors, while expansion of immature CD34 þ precursors occurs in high-grade MDS. On the basis of the number and severity of the phenotypic abnormalities detected, a scoring system is proposed that efficiently discriminates between normal/reactive and MDS CD34 þ HPC, the mean score significantly increasing from low-to high-grade MDS.

The effectiveness of antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia (ET) is not proven. In this study, the incidence rates of arterial and venous thrombosis were retrospectively analyzed in 300 lowrisk patients with ET treated with antiplatelet drugs as monotherapy (n ‫؍‬ 198) or followed with careful observation (n ‫؍‬ 102).

A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD341 cells and/or other major subsets of CD34 2 cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping.Methods: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease.Results: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low-versus high-grade cases. The most informative prognostic factors included the number of CD34 1 cells, presence of aberrant CD34 2 /CD117 1 precursors, decreased mature neutrophils and CD34 2 erythroid precursors, and increased numbers of CD36 2/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival.Conclusions: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival.

The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (Po0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.