| PUBLICATIONS (Ranked by impact factor of the journal) | LABORATORY RESEARCH The Ubiquitin Ligase FBXW7 Modulates Leukemia-Initiating Cell Activity by Regulating MYC Stability Missense FBXW7 mutations are prevalent in various tumors, including T cell acute lymphoblastic leukemia. To study the effects of such lesions, the authors generated animals carrying regulatable Fbxw7 mutant alleles. They showed that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes but spare normal hematopoietic stem cell function. [Cell] Abstract | Graphical Abstract | Press Release In Vivo Mapping of Notch Pathway Activity in Normal and Stress Hematopoiesis Researchers generated and describe animal models to identify and fate-map stem and progenitor cells expressing each Notch receptor, delineated Notch pathway activation, and performed in vivo gain- and loss-of-function studies dissecting Notch signaling in early hematopoiesis. These models provide comprehensive genetic maps of lineage-specific Notch receptor expression and activation in hematopoietic stem and progenitor cells. [Cell Stem Cell] Abstract | Graphical Abstract miR-9 Is an Essential Oncogenic MicroRNA Specifically Overexpressed in Mixed Lineage Leukemia-Rearranged Leukemia Acute myeloid leukemia (AML) with chromosomal translocations involving the mixed lineage leukemia (MLL) gene are usually associated with poor survival. Through a large-scale, genomewide microRNA expression assay, researchers showed that microRNA-9 (miR-9) is the most specifically up-regulated miRNA in MLL-rearranged AML compared with both normal control and non-MLL-rearranged AML. They demonstrated that miR-9 is a direct target of MLL fusion proteins and can be significantly up-regulated in expression by the latter in human and mouse hematopoietic stem/progenitor cells. [Proc Natl Acad Sci USA] Abstract IRP1 Regulates Erythropoiesis and Systemic Iron Homeostasis by Controlling HIF2a mRNA Translation Investigators showed that the disruption of mouse IRP1, but not IRP2, leads to profound HIF2a-dependent abnormalities in erythropoiesis and systemic iron metabolism. Thus, 4-6 week old IRP1-/- mice exhibit splenomegaly and extramedullary hematopoiesis, which is corrected in older animals. These erythropoietic abnormalities are caused by translational de-repression of HIF2a mRNA and subsequent accumulation of HIF2a, which induces expression of erythropoietin. [Blood] Abstract Notch1 Regulates AKT Activation Loop (T308) Dephosphorylation through Modulation of the PP2A Phosphatase in PTEN-Null T-Cell Acute Lymphoblastic Leukemia Cells Mutational loss of phosphatase and tensin homolog (PTEN) is frequent in T-cell acute lymphoblastic leukemia (T-ALL) and promotes resistance to ?-secretase inhibitors (GSIs) due to AKT activation. GSI treatments increased AKT-T308 phosphorylation and signaling in PTEN-deficient, GSI-resistant T-ALL cell lines, suggesting that Notch1-represses AKT independent of its PTEN transcriptional effects. [J Biol Chem] Abstract | Full Article Combining CAR T Cells and the Bcl-2 Family Apoptosis Inhibitor ABT-737 for Treating B-Cell Malignancy Chimeric antigen receptor (CAR) T cells targeting CD19 were generated from healthy donors as well as from precursor-B acute lymphoblastic leukemia patients and tested together with ABT-737 to evaluate apoptosis induction in five B-cell tumor cell lines. The CAR T cells were effective even if the cell lines exhibited different apoptosis resistance profiles, as shown by analyzing the expression of apoptosis inhibitors by PCR and western blot. [Cancer Gene Ther] Abstract Free Iron Catalyzes Oxidative Damage to Hematopoietic Cells/ Mesenchymal Stem Cells In Vitro and Suppresses Hematopoiesis in Iron Overload Patients Transfusional iron overload is of major concern in hematologic disease. Iron overload related dyserythropoiesis and reactive oxygen species (ROS) related damage to hematopoietic stem cell function are major setbacks in treatment of such disorders. Scientists therefore aimed to investigate the effect of iron overload on hematopoiesis of patients and explore the role of ROS in iron induced oxidative damage in hematopoietic cells and microenvironment in vitro. [Eur J Haematol] Abstract CLINICAL RESEARCH Impaired B-Cell Reconstitution in Children after Chemotherapy for Standard or Medium Risk Acute Precursor B-Lymphoblastic Leukemia Immune reconstitution was studied in a homogenous cohort of 48 children with standard- or medium-risk acute lymphoblastic leukemia (ALL) treated according to the ALL-BFM-protocol. Whereas the T-cell compartment is only moderately affected and recovered to normal levels quickly after treatment cessation, B-cells are significantly reduced during and after therapy. Especially the naïve B-cell compartment declines. [Leuk Lymphoma] Abstract Usefulness of Allogeneic Hematopoietic Stem Cell Transplantation in First Complete Remission for Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm with Skin Involvement: A Case Report and Review of Literature The authors treated with acute lymphoblastic leukemia-type regimen for a child with blastic plasmacytoid dendritic cell neoplasma (BPDCN) with skin and leukemic involvement. She has been disease-free for 4 years after allogeneic bone marrow transplantation in first complete remission. In 33 cases of pediatric BPDCN, the over survival was significantly lower in the patients with skin manifestation than those without cutaneous involvement. [Pediatr Blood Cancer] Abstract |
| SCIENCE NEWS | CTI Announces New Data Demonstrating the Safety and Tolerability Profile of Pacritinib in Patients with Myelofibrosis Cell Therapeutics, Inc. (CTI) announced results from a pooled analysis of data from completed Phase I and II studies of pacritinib, an oral JAK2/FLT3 inhibitor, demonstrating the safety and tolerability profile of pacritinib in patients with myelofibrosis. An integrated safety analysis of four completed Phase I and II studies totaled 191 patients who were treated with pacritinib for myeloid, primarily myelofibrosis, or lymphoid malignancies to quantify clinical toxicities, with a focus on hematologic effects. [Press release from Cell Therapeutics, Inc. discussing research presented at the 18th Congress of the European Hematology Association, Stockholm] Press Release Alnylam Scientists Present Pre-Clinical Data with ALN-CC5, an RNAi Therapeutic Targeting Complement Component C5 for the Treatment of Complement-Mediated Diseases Alnylam scientists presented pre-clinical results showing potent, dose-dependent, and durable RNAi-mediated knockdown of serum C5 and inhibition of complement-mediated hemolytic activity of approximately 90% with a subcutaneously administered RNAi therapeutic. [Press release from Alnylam Pharmaceuticals, Inc. discussing research presented at the 6th International Conference on Complement Therapeutics, Kos] Press Release Affimed Reports Phase I Clinical Data for Its Immunotherapy AFM13 in Relapsing/Refractory Hodgkin Lymphoma Patients Affimed Therapeutics AG announced encouraging results from a phase I clinical trial of AFM13 as monotherapy for the treatment of patients with advanced relapsing/refractory Hodgkin lymphoma. AFM13 appears to be well tolerated with evidence of meaningful anti-tumor activity, including partial responses and stable diseases. AFM13 is a bispecific TandAb antibody recruiting host NK cells via its CD16A-binding domains to engage and kill CD30-positive malignant cells. [Press release from Affimed Therapeutics AG discussing research presented at the 12th International Conference on Malignant Lymphoma, Lugano] Press Release From our sponsor: Free mouse hematopoietic progenitors wallchart. Request your copy. |
| INDUSTRY NEWS | FDA Puts Cell Therapeutics Blood Cancer Drug on Hold after Death from Myocarditis Cell Therapeutics Inc said the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on the company’s experimental blood cancer drug after the death of a patient. The patient, being treated with the drug tosedostat in combination with a chemotherapy drug, died of myocarditis, or infection of the heart muscle, the company said in a regulatory filing. [Thompson Reuters] Press Release MEI Pharma Initiates Phase II Clinical Trial of Pracinostat and Vidaza® in Frontline Myelodysplastic Syndrome MEI Pharma, Inc. announced that the first patients have been dosed in a Phase II clinical trial of its lead drug candidate Pracinostat in combination with Vidaza (azacitidine) in patients with previously untreated intermediate-2 or high-risk myelodysplastic syndrome (MDS). The randomized, double-blind trial is designed to evaluate the safety and efficacy of Pracinostat compared to placebo when combined with Vidaza, a drug approved by the U.S. Food & Drug Administration for the treatment of MDS. [MEI Pharma, Inc.] Press Release Celebrating 25 Years and Counting: Leukemia and Lymphoma Society’s “Team In Training” Goes the Distance and Beyond for Blood Cancer Patients This year alone, The Leukemia & Lymphoma Society (LLS) is supporting more than 300 research projects with one goal in mind: Discovering lifesaving therapies for blood cancer patients. And in 2013, “Team In Training” (TNT), a flagship LLS fundraising campaign and the world’s first and largest endurance sports training program, is marking its landmark 25th anniversary. To date, TNT has helped LLS invest more than $875 million in research to discover and deliver breakthrough cancer treatments that are saving lives today. [PR Newswire Association, LLC] Press Release |
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