LABORATORY RESEARCH Somatic Deletions of Genes Regulating MSH2 Protein Stability Cause DNA Mismatch Repair Deficiency and Drug Resistance in Human Leukemia Cells Findings reveal a previously unrecognized mechanism whereby somatic deletions of genes regulating MSH2 degradation result in undetectable levels of MSH2 protein in leukemia cells, DNA mismatch repair deficiency and drug resistance. [Nat Med] Abstract | Press Release Inhibition of Rac GTPase Signaling and Downstream Pro-Survival Bcl-2 Proteins as Combination Targeted Therapy in MLL-AF9 Leukemia Using an in vivo gene targeting approach, researchers demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. [Blood] Abstract Induction of Erythropoiesis Using Human Vascular Networks Genetically-Engineered for Controlled Erythropoietin Release Here, investigators have genetically-engineered human blood-derived endothelial colony-forming cells to express erythropoietin (EPO) under control of a tetracycline-regulated system, and generated subcutaneous vascular networks capable of systemic EPO release in immunodeficient mice. [Blood] Abstract Methionine Aminopeptidase 2 Is Required for Hematopoietic Stem Cell Initiation and Proliferation Scientists investigated the role of methionine aminopeptidase II in hematopoiesis using zebrafish embryo and human umbilical cord blood models. [Blood] Abstract Distinct Classes of c-Kit Activating Mutations Differ in their Ability to Promote RUNX1-ETO-Associated Acute Myeloid Leukemia To test whether distinct subtypes of activating c-KIT mutations differ in their leukemogenic potential in association with RUNX1-ETO, researchers used a retroviral transduction/transplantation model to co-express RUNX1-ETO with either c-KitD814V or c-KitT417IΔ418-419 in murine hematopoietic stem/progenitor cells used to reconstitute lethally irradiated mice. [Blood] Abstract Inducible Knockout of GRP78/BiP in the Hematopoietic System Suppresses Pten-Null Leukemogenesis and AKT Oncogenic Signaling To directly elucidate the requirement of GRP78 in leukemogenesis, scientists created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. [Blood] Abstract p38α Controls Erythroblast Enucleation and Rb Signaling in Stress Erythropoiesis Here, investigators show that p38α, a mitogen-activated protein kinase, is required for erythroid enucleation. [Cell Res] Abstract Targeted Disruption of the CCR5 Gene in Human Hematopoietic Stem Cells Stimulated by Peptide Nucleic Acids The work suggests a therapeutic strategy for CCR5 knockout in hematopoietic stem cells from HIV-1-infected individuals, rendering cells resistant to HIV-1 and preserving immune system function. [Chem Biol] Abstract CLINICAL RESEARCH Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts Researchers used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. [New Engl J Med] Abstract | Press Release A Phase II Multicenter Study of Lenalidomide in Relapsed or Refractory Classical Hodgkin Lymphoma In a multicenter phase II study, the efficacy of lenalidomide in relapsed or refractory classical Hodgkin lymphoma patients was evaluated at a dose of 25 mg on days 1-21 of a 28-day cycle. [Blood] Abstract High BRE Expression Predicts Favorable Outcome in Adult Acute Myeloid Leukemia, in Particular Among MLL-AF9 Positive Patients Investigators studied whether expression changes of over 1600 ubiquitination related genes correlated with clinical outcome in 525 adult acute myeloid leukemia patients. [Blood] Abstract |