LABORATORY RESEARCH Autoantigen Can Promote Progression to a More Aggressive TCL1 Leukemia by Selecting Variants with Enhanced B-Cell Receptor Signaling (Auto)antigen engagement by the B-cell receptor and possibly the sites where this occurs influence the outcome of chronic lymphocytic leukemia. To test if selection for autoreactivity leads to increased aggressiveness and if this selection plays out equally in primary and secondary tissues, researchers used T-cell leukemia (TCL)1 cells reactive with the autoantigen phosphatidylcholine. [Proc Natl Acad Sci USA] Abstract | Full Article Transposon Mutagenesis Reveals Cooperation of E-Twenty-Six Family Transcription Factors with Signaling Pathways in Erythro-Megakaryocytic Leukemia To define genetic lesions driving leukemia, the authors targeted cre-dependent Sleeping Beauty transposon mutagenesis to the blood-forming system using a hematopoietic-selective vav 1 oncogene promoter. [Proc Natl Acad Sci USA] Abstract mTOR Regulates DNA Damage Response through NF-κB-Mediated FANCD2 Pathway in Hematopoietic Cells Researchers showed that gene targeting of mammalian target of rapamycin (mTOR) in hematopoietic stem/progenitor cells causes a defective DNA damage response (DDR) to a variety of DNA damage agents, mimicking that caused by deficient FANCD2, a key component of the Fanconi anemia (FA) DDR machinery. [Leukemia] Abstract Global H3K4me3 Genome Mapping Reveals Alterations of Innate Immunity Signaling and Overexpression of JMJD3 in Human Myelodysplastic Syndrome CD34+ Cells Data indicate the deregulation of trimethylated histone 4 lysine 3 (H3K4me3) and associated abnormal activation of innate immunity signals play a role in the pathogenesis of myelodysplastic syndromes (MDS) and that targeting these signals may have potential therapeutic value in MDS. [Leukemia] Abstract Inosine Triphosphate Pyrophosphohydrolase (ITPA) Polymorphic Sequence Variants in Adult Hematological Malignancy Patients and Possible Association with Mitochondrial DNA Defects Investigators hypothesized that reduced ITPA activity may cause acquired mitochondrial DNA (mtDNA) defects. Furthermore, they investigated whether accumulating mtDNA defects may then be a risk factor for cell transformation, in adult hematological malignancy. [J Hematol Oncol] Abstract | Full Article The Src Homology 2 Protein Shb Promotes Cell Cycle Progression in Murine Hematopoietic Stem Cells by Regulation of Focal Adhesion Kinase Activity The widely expressed adaptor protein Shb has previously been reported to contribute to T cell function due to its association with the T cell receptor and furthermore, several of Shb’s known interaction partners are established regulators of blood cell development and function. Researchers explored hematopoietic stem and progenitor cell function in the Shb knockout mouse. [Exp Cell Res] Abstract Electrospun Nanofibers as a Bioadhesive Platform for Capturing Adherent Leukemia Cells Researchers investigated the adhesive behaviors of normal and abnormal hematopoietic cells on nanotopographical materials. Previously, electrospun nanofiber scaffolds (NFS) were used to capture and expand hematopoietic stem cells in vitro; here they demonstrated that NFS could also serve as a useful bioadhesive platform for capturing functionally adherent leukemia cells. [J Biomed Mater Res A] Abstract CLINICAL RESEARCH MRD-Directed Risk-Stratification Treatment May Improve Outcome of t (8;21) AML in the First Complete Remission: Results from AML05 Multicenter Trial Researchers aimed to improve outcome of t (8;21) acute myeloid leukemia (AML) in first complete remission by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. [Blood] Abstract A Variant in IRF3 Impacts on the Clinical Outcome of AML Patients Submitted to Allo-SCT Scientists analyzed two gene variants in IFN regulatory factor-3 (IRF3) (rs7251 and rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical sibling allo-SCT. [Bone Marrow Transplant] Abstract Etoposide in Combination with Low-Dose CAG (Cytarabine, Aclarubicin, G-CSF) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia: A Multicenter, Randomized Control Trial in Southwest China In a well-controlled multi-center randomized trial in southwestern China, 228 patients with refractory or relapsed acute myeloid leukemia received a low-dose CAG regimen either with etoposide or without etoposide. The complete remission rate, overall survival and toxicity were evaluated. [Leuk Res] Abstract |