A Tefferi

....

....

..Our observations suggest that IDH mutations in PMF are independent predictors of leukemic transformation and raise the possibility of leukemogenic collaboration with JAK2V617F...

..Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest...

..Treatment with busulfan or interferon-α is usually effective in hydroxyurea failures. Screening for clinically significant AvWS is recommended before administrating aspirin in the presence of extreme thrombocytosis...

..The present study examined whether attendance at medical grand rounds increased after providing complimentary food to attendees and also assessed attendee attitudes about complimentary food...

..The current prospective study addresses this issue in the context of currently accepted independent prognostic variables...

....

..The current review highlights these changes and also provides diagnostic algorithms that are tailored to routine clinical practice...

..Taken together, these observations suggest that JAK2(V617F) is an acquired myeloid lineage-specific mutation that engenders a pathogenetic relevance for the PV phenotype in MPD...

..Allogeneic transplantation offers a viable treatment option for drug-refractory cases...

..In this article, we outline contemporary diagnostic algorithms for each of these disorders and provide an evidence-based approach to management...

....

..Additional patient management issues are raised during systemic anticoagulation and surgery. This review summarizes putative pathogenetic mechanisms of bleeding and their management in ET and PV...

..We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype...

..05). We conclude that TET2 mutations occur in both JAK2V617F-positive and -negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance...

..98). We conclude that TET2 mutations are frequent in SM, segregate with KITD816V and influence phenotype without necessarily altering prognosis...

..This preliminary report suggests a potential value for array CGH in terms of both clinical diagnostics and genomic research in MPNs...

..Cladribine has been shown to be effective in patients who develop resistance to interferon treatment...

....

..The bone marrow histologic phenotype of these imatinib-sensitive eosinophilic disorders includes systemic mastocytosis, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, and atypical chronic myeloproliferative disorder...

..However, compared with the PRV-1 assay, mutation screening for JAK2(V617F) displayed greater accuracy in distinguishing PV from SP...

..Despite recent progress in the field, several important issues remain controversial. In this review, we will present the areas of agreement, but also point out where the authors' personal viewpoints differ...

..The current communication features a comprehensive clinical summary of both secondary and primary eosinophilic disorders with emphasis on recent developments in molecular pathogenesis and treatment...

..Whether the presence of this specific mutation or its allele burden modifies the risk of thrombosis in patients with MPDs currently is under investigation...

..Such progress is paving the way for a transition from a histologic to a semi-molecular classification system that preserves conventional terminology, while incorporating new information on molecular pathogenesis...

..Recent discoveries of myeloproliferative-disease-specific molecular markers, including the JAK2 V617F tyrosine kinase mutation that is found in the majority of patients with PV, provide further support for such a measure...

....

..Two other PSSs, Cervantes and Mayo, were recently reported as being more useful in younger patients. The current study compares these 3 PSSs among all age groups...

..Bone marrow histologic and hematologic remissions characterize CR and CR/PR, respectively. The panel agreed that the CI response category is applicable only to patients with moderate to severe cytopenia or splenomegaly...

....

..In the current study, we show that microcytosis is a frequent laboratory feature in agnogenic myeloid metaplasia and investigate its clinical relevance in the particular setting...

..This latter phenomenon, through neutrophil-derived elastase, could also underlie the abnormal peripheral-blood egress of myeloid progenitors in MMM...

..Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study...

..Advances have also been meager in terms of treatment for disease complications, including anemia, splenomegaly, and leukemic transformation...

....

..Therefore, mutation screening for JAK2V617F can be considered as a myeloid-specific clonality assay and it is diagnostically most useful in the evaluation of "polycythemia"...

..We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities...

..This review discusses how this process is unfolding in myeloproliferative disorders...

..This review outlines a practical approach to diagnosis, in addition to treatment of life-threatening and non-life-threatening complications of PV...

..The revised WHO document continues to promote the recognition of histologic categories as a necessary first step toward the genetic characterization of myeloid malignancies...

..Treatment with busulfan or interferon-a is usually effective in hydroxyurea failures...

..This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance...

..The unmet need for treatment in PMF dictates a different approach for assessing the therapeutic value of new drugs (eg, JAK inhibitors, pomalidomide) or allogeneic stem-cell transplantation...

..Here we describe a patient who developed pneumomediastinum, pneumopericardium, subcutaneous emphysema and pneumothorax secondary to severe bronchiolitis obliterans complicating the post bone marrow transplantation course...

..The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes...

..However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation...

..Clinicopathologic correlates to these biologic parameters are currently being defined...

..Current information on mutational status and response to JAK2 inhibitor drug therapy is too preliminary to draw any conclusions...

..We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes...

..Allelic distortion from acquired uniparental disomy contributes to the appearance of a more pronounced effect on disease susceptibility in VF-positive patients, when studying clonally affected tissue...

..However, their value is undermined by their respective potential to cause peripheral neuropathy and myelosuppression. We therefore evaluated the safety and therapeutic activity of another immunomodulatory drug, pomalidomide...

..The practice of en bloc screening for JAK2V617F, JAK2 exon 12, and MPL mutations is scientifically irrational and economically irresponsible...

..This review discusses some of the current and past observations regarding the pathogenesis of chronic myeloproliferative disorders...

..In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit...

..The control of splenomegaly may not be durable, and the likelihood of leukemic progression or death is not dramatically lowered...

..To describe presenting clinical manifestations, long-term disease complications, prognostic indicators, and outcome of pregnancy for women younger than 50 years with essential thrombocythemia...

..New treatment approaches include the use of thalidomide alone or in combination with prednisone and hematopoietic stem cell transplantation...

....

..Furthermore, randomized, prospective, and controlled retrospective data have provided additional clinical information that has resulted in the development of risk categories and risk-adjusted treatment recommendations...

..It is our impression that many more JAK inhibitors need to be evaluated in order to identify the best-in-class in terms of efficacy, toxicity and suitability for future combination treatment programs...

....

....

..In contrast, only 40% partial response rate was seen in 10 HES cases. FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis...

..Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance rational therapy decisions in SMCD...

..The study also suggests either a megakaryocyte origin or a megakaryocyte effect for the putative angiogenic cytokine...

..Therefore, although the presence of JAK2(V617F) in ET appears to promote a PV phenotype, it might not carry treatment-relevant information...

..Clinical responses did not correlate with improvements in either intramedullary fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears to be a promising drug regimen for treating cytopenias in patients with MMM...

..This study shows a relatively high incidence of IDH mutations in blast-phase MPN, regardless of JAK2 mutational status, and the occurrence of similar mutations in chronic-phase PMF...

..In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase...

....

..A possible association with thrombotic complication has also been considered...

..The current study was designed to provide additional data in this regard...

..Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon...

..Consistent with previous observations in animal models, our observations suggest the possibility that altered TPO regulation resulting in sustained ligand excess may have pathogenetic relevance in MMM...

..Additional important prognostic factors not taken into account by the IPSS include the baseline erythrocyte indices, lymphocyte count, and clonal burden...

..02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV...

..These results are contrary to previous reports that suggested inferior survival as well as poor response to alpha interferon therapy in CML patients carrying der(9) deletions...

..86% test accuracy). The current study suggests that PRP serotonin concentration might be considered as one of the several biological markers that complement each other for the diagnosis of PV...

..The current study highlighted the prognostic relevance of leucocytosis on various aspects of the disease in PV...

..The new system displayed a stronger discriminative value, between risk categories, compared with currently existing prognostic models...

..We conclude that neither the SCLL phenotype nor blood eosinophilia is a consistent feature of FGFR1-associated 8p11.2 translocations; conversely, FISH might not always reveal FGFR1 involvement in typical SCLL...

..These observations suggest that clonal myelopoiesis antedates acquisition of JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho-myeloid progenitor cell...

..The current study provides direct evidence for the clonal involvement of both B and T lymphocytes in MMM. A larger study is needed to clarify the relevance of the observed interpatient heterogeneity in clonal constitution...

..In patients with clonal eosinophilic disorders and mast cell disease, the use of molecular diagnostics to identify novel mutations and gene rearrangements, has resulted in superior diagnostic and therapeutic strategies...

..We conclude that MPLW515L/K and JAK2V617F are both early events in MMM and allele burden, rather than the mere presence of these mutations, might be relevant to phenotypic variation in myeloproliferative disorders...

..Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations...

..03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD...

....

..The current prospective study does not support an independent prognostic value for PB CD34 count in MMM...

..The current observation strengthens the specific association between JAK2 V617F and classic MPD, but also suggests an infrequent occurrence in other myeloid disorders...

..In SMCD, the presence of D816V mutation was significantly associated with advanced age, an aggressive clinical course, increased bone marrow mast cell content, and chronic myelomonocytic leukemia...

..These issues are discussed within the context of clinical practice...

..Myocardial biopsy revealed eosinophilic infiltration and degranulation, and the cardiogenic shock was reversed with the prompt institution of corticosteroid therapy...

..In contrast, BM angiogenesis, reticulin fibrosis, and levels of MC mediators showed no prognostic relevance...