LABORATORY RESEARCH Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo Investigators described a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia. The expression of protein kinase C-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. [Cancer Cell] Full Article The Rac GTPase Effector p21 Activated Kinase Is Essential for Hematopoietic Stem/Progenitor Cell Migration and Engraftment Using conditional knock-out mice, researchers demonstrated that among group A p21 activated kinases (PAKs), Pak2-/- hematopoietic stem and progenitor cell (HSPC) show reduced homing to the bone marrow and altered cell shape similar to Pak Inhibitory Domain-Lin–Sca1+c-kit+ cells in vitro and are completely defective in HSPC engraftment. [Blood] Abstract Glypican-3 Mediated Inhibition of CD26 by TFPI: A Novel Mechanism in Hematopoietic Stem Cell Homing and Maintenance CD26 is a widely expressed membrane-bound ectopeptidase that cleaves CXCL12 thereby depleting its chemokine activity. The authors identified tissue factor pathway inhibitor (TFPI) as a biological inhibitor of CD26 in murine and human hematopoietic stem/progenitor cells. [Blood] Abstract Inhibition of Intracellular Dipeptidyl Peptidases 8 and 9 Enhances Parthenolide’s Anti-Leukemic Activity Parthenolide is selectively toxic to leukemia cells; however, it also activates cell protective responses which may limit its clinical application. Therefore, scientists sought to identify agents that synergistically enhance parthenolide’s cytotoxicity. [Leukemia] Abstract Tenovin-D3, a Novel Small-Molecule Inhibitor of Sirtuin SirT2, Increases p21 (CDKN1A) Expression in a p53-Independent Manner Recent studies demonstrated that tenovin-6, a small molecule inhibitor of sirtuins SirT1 and SirT2, reduces tumor growth in vivo and eliminates leukemic stem cells in a murine model for chronic myelogenous leukemia. Here, researchers described a tenovin analog, tenovin-D3, that preferentially inhibits sirtuin SirT2 and induces predicted phenotypes for SirT2 inhibition. [Mol Cancer Ther] Abstract Hoxa9 Transduction Induces Hematopoietic Stem and Progenitor Cell Activity through Direct Down-Regulation of Geminin Protein Researchers found that retroviral transduction-mediated overexpression or siRNA-mediated knock-down of Hoxa9 respectively down-regulated or up-regulated Geminin in hematopoietic cells. [PLoS One] Full Article Combination of Guanine Arabinoside and Bcl-2 Inhibitor YC137 Overcomes the Cytarabine Resistance in HL-60 Leukemia Cell Line Investigators established a new cytarabine (ara-C)-resistant acute myeloid leukemia cell line (HL-60/ara-C60) with dual resistance characteristics of the anti-antimetabolic character of decreased ara-C triphosphate production and an increase in the antiapoptotic factors Bcl-2 and Bcl-XL. [Cancer Sci] Abstract CLINICAL RESEARCH Impact of Malignant Stem Cell Burden on Therapy Outcome in Newly Diagnosed Chronic Myeloid Leukemia Patients Researchers prospectively analyzed the proportion of Philadelphia chromosome positive leukemic stem and progenitor cells from 46 newly diagnosed chronic myeloid leukemia patients both at the diagnosis and during imatinib or dasatinib therapy. [Leukemia] Abstract A Phase Ib GOELAMS Study of the mTOR Inhibitor RAD001 in Association with Chemotherapy for AML Patients in First Relapse The authors conducted a Phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse. [Leukemia] Abstract |