Mario Cazzola

..This observation is relevant to genetic counseling, emphasizing the importance of gene-based diagnosis...

..WPSS predicts survival and leukemia progression at any time during follow-up, and may therefore be used for implementing risk-adapted treatment strategies...

..Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective...

..These genetic disorders should be taken into account in the differential diagnosis of unexplained hyperferritinaemia...

..Since comorbidities have a significant impact on the outcome of patients with MDS, accounting for both disease status and comorbid conditions considerably improves risk stratification...

..These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia...

..Heterozygosity for the ferroportin Val 162 deletion represents the prototype of selective reticuloendothelial iron overload, and should be taken into account in the differential diagnosis of hereditary or congenital hyperferritinaemias...

..It is hoped that these advances will soon translate into improved therapeutic approaches...

..003), and anaemia (P < 0.001) independently correlated with MVD. In summary, this study indicates that assessment of BM angiogenesis, as measured by MVD, may be a useful additional tool in the histopathological definition of CMD...

..We, therefore, studied the relationship between severity of anemia and outcome in myelodysplastic syndrome patients...

..In conclusion, leukocytosis at diagnosis of PV is a risk factor for evolution in post-PV MF. A dynamic score based on hemoglobin level, and platelet and leukocyte count predicts survival at any time from diagnosis of post-PV MF...

..Thus, a genetic predisposition to acquisition of JAK2 (V617F) is inherited in families with myeloproliferative disorders...

..Accounting for both disease status by means of the WPSS and comorbidity through the MDS-CI considerably improves risk stratification in myelodysplastic syndromes...

..JAK2 (V617F)-positive ET may evolve in few instances into JAK2-negative leukemia. The outcome of patients is poor whatever the treatment used...

..However, familial clustering is reported. The purpose of this study was to assess the prevalence and the clinical phenotype of familial CMDs, and to study the anticipation of disease onset in successive generations...

..MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable...

....

..This exemplifies a novel paradigm in which a somatic gain-of-function mutation is initially responsible for clonal expansion of hematopoietic cells and later for their abnormal trafficking via an activated cell progeny...

..To assess life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia...

..The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments...

..We studied bone marrow (BM) histologic abnormalities in myelodysplastic syndromes (MDS) classified according to WHO criteria to determine their clinical correlates and prognostic value...

....

..In MDS, the detection of MMP deregulated expression may be important also from the clinical point of view: it may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments...

..87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase...

..Thus, enumeration of circulating CD34-positive cells may be useful in the work-up of patients with myeloproliferative disorders...

....

..Acute leukemia (AL) may occur as rare and late event of polycythemia vera (PV)...

..In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker...

..Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS...

..This case points to the importance of suspecting pulmonary EMH when unexplained progressive dyspnea occurs in a patient with MMM. Early recognition of pulmonary EMH may prevent PH and favor a better response to therapy...

..81 for intermediate-2 according to the age-adjusted DIPSS. The novelty of these models is the prognostic assessment of patients with PMF anytime during their clinical course, which may be useful for treatment decision-making...

..Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment...

..In 3 cases carrying double MPL mutations, deep sequencing analysis showed identical load and location in cis of the paired lesions, indicating their simultaneous occurrence on the same chromosome...

....

..From a clinical viewpoint, neutrophil CD177 mRNA overexpression is rather a marker of abnormal neutrophil production and/or release in patients with CMD...

..A relationship was found between JAK2 (617V>F) and fetal loss (P = .05). This study indicates that patients carrying the JAK2 (617V>F) mutation have higher risk of developing pregnancy complications...

..Moreover, a genetic predisposition to acquisition of different JAK2 mutations is inherited in families with myeloproliferative disorders...

..Second, this observation supports the hypothesis that reticuloendothelial iron overload in patients with ferroportin disease is caused by loss-of-function mutations in the SLC11A3 gene that mainly impair macrophage iron recycling...

..Its abnormal expression also in MDS may play a role in promoting aberrantly increased cell viability and contribute to the altered homeostatic balance between cell growth and cell death...

..These findings suggest that, despite the phenotypical difference, the outcome of JAK2 exon 12 mutations-positive PV is similar to that of JAK2 (V617F)-positive PV...

..013). These observations suggest that patients with SF3B1 mutation have inappropriately low hepcidin levels, which may explain their propensity to parenchymal iron loading...

..On the other hand, JAK inhibitors have not thus far shown disease-modifying activity therefore any other deduction on these new drugs seems premature...

..Anaemia is often observed in patients with chronic heart failure (CHF), and it may be associated with a worse prognosis. Aim of this study was to identify the individual mechanisms of anaemia in CHF patients...

..The hematologic passport should be used within a global strategy to deter blood doping...

..A double-gradient denaturing gradient gel electrophoresis (DG-DGGE) method easily detected the above deletion...

..The assessment of SF3B1 mutation status may become innovative diagnostic and prognostic tools and the availability of spliceosome modulators opens novel therapeutic prospects...

....

..We conclude that the BRAF V600E mutation is present in all patients with HCL and that, in combination with clinical and morphologic features, represents a reliable molecular marker for this condition...

..Am. J. Hematol. 2011. © 2011 Wiley Periodicals, Inc...

..This exemplifies a new paradigm in which mutations in mRNA cis-acting elements may be responsible for phenotypic variability in disease states...

..INTERPRETATION AND CONCLUSIONS: Using evidence and consensus, recommendations for the treatment of MDS were issued. Statements were graded according to the strength of the supporting evidence and uncertainty was explicitly declared...

..The low cumulative 10-year risk of thrombosis, leukaemia and solid tumours indicates that pipobroman is an adequate treatment for patients with high risk ET...

..To assess the effect of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) treatment on survival and leukemic transformation in myelodysplastic syndrome (MDS)...

..In conclusion, aberrant MtF expression in RARS erythroblasts occurs at a very early stage of erythroid differentiation and is paralleled by an up-regulation of genes involved in this process...

..Mutations either generate premature termination codons or were missense substitutions, affecting highly conserved residues, relevant to the protein structure and/or function...

..The regulation of MtF expression and possible therapeutic applications of MtF in neurological disorders involving increased iron deposition are topics for future research...

..Our results clarify the natural history of the disease and are compatible with the hypothesis that the HFE2 gene has greater influence on iron absorption than other haemochromatosis-associated genes...

..This condition should be considered not only in families with autosomal iron overload or hyperferritinaemia, but also in cases of unexplained hyperferritinaemia...

..This HHCS is associated with mutations in the gene of ferritin subunit L, located in chromosome 19. We describe 2 new families with HHCS, one of them presenting a new L-ferritin mutation (A37T: -Zaragoza-)...

..This study suggests that several of the genes mapping to the CDR of the 5q- syndrome play a role in the pathogenesis of this disorder...

..This study provides important and new insights into the pathophysiology of MDS...

..All these microbial agents probably interfere with complex immunological pathways, thus contributing to induce and exacerbate asthma in genetically predisposed individuals...

....

....

..This pilot study represents a first step toward developing a diagnostic microchip for large-scale analyses for epidemiological studies and screening of mutations associated with iron disorders...

....

..Obviously, these antibiotics must be reserved only to cases of documented ineffectiveness of the common antimicrobial agents...

..Differences between the two treatments were not statistically significant (P>0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage...

..Recommendations should be applied in the context of the WHO classification...

..The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases...

..This confirms that, in heterozygous individuals, beta-thalassaemia intermedia may be caused by inactivation of the beta-locus in trans as a result of chromosome 11p15.5 deletions in a subpopulation of haematopoietic cells...

....

..These data provide an important link between inherited and acquired forms of sideroblastic anemia and indicate that ABCB7 is a strong candidate gene for RARS...

..The only limits set for the development of a LABA with a new product profile are medical needs and marketing opportunities...

..We identified a new mutation (C70R), which affects 1 of the 8 conserved cysteines that form the disulfide bonds and are critical for the stability of the polypeptide...

..Dosage was determined by baseline liver iron concentration (LIC)...

....