Alan F List

..The importance of new advances in myelodysplastic syndrome will be discussed in this review...

..This review presents the data related to iron overload in MDS, including its prevalence, diagnosis, clinical impact, and management...

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..We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN...

..This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1-risk myelodysplastic syndrome (MDS)...

..The current active treatment paradigm for MDS incorporates the most recent strategies yielding improved disease outcomes and patient survival...

..Combination strategies are now in both MDS and AML that could further broaden the therapeutic potential of lenalidomide...

..Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc...

..This article reviews the clinical experience with lenalidomide, highlighting recent understanding of the dual karyotype-dependent mechanisms of action...

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..The benefits of lenalidomide plus rhu-EPO are currently under investigation in a phase 3 Eastern Cooperative Oncology Group (ECOG)-sponsored intergroup study. This study is registered at www.clinicaltrials.gov as NCT00910858...

..The authors evaluated predictive factors in patients with secondary AML treated with anthracycline-based induction therapy...

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..2% for MEC (P=0.09), with median OS of 11 and 4.5 months, respectively (P=0.07). In first relapse, CR was 36.8% and 25.9% (P=0.35) and median OS was 6.7 and 6.7 months, respectively (P=0.87). Our data support use of CLAG for RR-AML...

..Based on these findings, Treg(EM) cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes...

..This discussion examines the current NCCN guidelines for the treatment of these patients, including the management of anemia in lower-risk MDS, and discusses the potential future therapeutic applications of lenalidomide in this disease...

..Our study is the first to demonstrate that JAK2-V617F signalling is dependent on lipid rafts and that statins may be effective in a potential therapeutic approach for MPNs...

..Taken together, our findings indicate that HG-829 is a potent, long-acting, and noncompetitive modulator of P-glycoprotein export function that may offer therapeutic promise for multidrug-resistant malignancies...

..We highlight the mechanism of action and the recent advances in understanding the biology of del (5q) MDS. We also explore its potential use and the efforts to further improve its activity in non-del (5q) MDS...

..We discuss herein the current understanding of the biology of the 5q- syndrome, actions of efficacy of lenalidomide and strategies for clinical management...

..We use a case-based format to discuss current options for treatment, including erythropoiesis-stimulating agents, hypomethylating agents, lenalidomide, immunosuppressive therapy, supportive care, and investigational agents...

..The most common adverse reactions include dose-dependent neutropenia and thrombocytopenia that are more pronounced in patients with del(5q) in whom early suppression of the clone is expected...

..We applied the MDAS to Moffitt Cancer Center (MCC) MDS patients to validate its prognostic utility...

..Finally, we highlight the current understanding of its mechanism of action, discussing the emerging insight into the underlying biology of del(5q) MDS and its linkage to potential targets of lenalidomide...

..8 months. Overall survival from diagnosis to the last follow-up in patients with LC was 28.2 months, shorter than patients without LC (44 months). LC and its equivalent could predict disease progression to AML...

..With the emerging data elucidating the pathogenesis of the 5q- syndrome and the success of clinical trials, a cohesive story connecting the biology and pharmacology associated with this subtype of myelodysplastic syndromes has emerged...

..While most non-registered MDS patients showed resource utilization and survival characteristics consistent with lower-risk MDS, a subset was registered as acute myeloid leukemia (7.6%) and accounted for early mortality...

..The National Comprehensive Cancer Network Clinical Practice Guidelines recently added lenalidomide to the therapeutic algorithm for MDS as front-line therapy for lower-risk MDS patients with del(5q) and transfusion-dependent anemia...

..Of the MPNs, MF presents with the most severe morbidity and greatest mortality. Although the cause of MF is unknown, it is thought to occur from acquired mutations that target the hematopoietic stem cell...

..These data establish a critical role for MR in recruitment and assembly of Epo-R and signal intermediates into discrete membrane signaling units...

..Future studies are needed to further investigate constitutional telomere attrition as a possible predisposing factor for MDS...

..A phase III Intergroup trial (ECOG 2905) will test the capacity to potentiate erythropoietin response by comparing response to lenalidomide monotherapy to the combination of darbepoetin and lenalidomide in non-deletion 5q MDS patients...

..MDS became reportable to the Surveillance, Epidemiology, and End Results Program (SEER) in 2001. We report first study of MDS among large population in the Veteran Affair system...

..The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics...

..Our pilot study suggested that analysis of microRNA expression profile offers diagnostic utility, and provide pathogenetic and prognostic discrimination in MDS...

..MDS incidence rates significantly increased with calendar year in 2001 through 2004, and only 4% of patients were reported to registries by physicians' offices. Thus, MDS disease burden in the United States may be underestimated...

..An immune-mediated mechanism is likely to contribute to MDS early after diagnosis. New approaches that interfere with inflammatory pathways in the bone marrow microenvironment may move closer toward sustained disease control in MDS...

..90% P-gp inhibition was achieved within 2h at a plasma threshold of 132 ng/ml zosuquidar. The recommended phase II dose of zosuquidar is 700 mg/day...

..Evasion of NK immunosurveillance may have importance for MDS disease progression...

..These data indicate that Src-STAT5 and Src-Akt pathways are integral survival signal pathways in AML cells. Src inhibition may represent a novel treatment strategy for investigation in AML...

..These results support day 90 hypoalbuminemia as an adverse prognostic marker for NRM and OS after allo-HCT for acute myelogenous leukemia and myelodysplastic syndrome...

..In this review, data accumulated in the US, Europe, and Asia will be summarized to provide insight and direction for a multi-center international trial...

..Multicenter phase II and III studies are under way to further assess the erythroid and cytogenetic response rates in distinct subtypes of MDS, including 5q- deletion, and to optimize its clinical application...

..The proposed investigations should provide important insight into mechanism of disease biology and the development of novel more effective therapeutics. ..

..The proposed investigations should provide important insight into mechanism of disease biology and the development of novel more effective therapeutics. ..