PAR1 Signaling Regulates the Retention and Recruitment of EPCR-Expressing Bone Marrow Hematopoietic Stem Cells Scientists report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR+) long-term repopulating hematopoietic stem cells in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). [Nat Med] Abstract New IDH1 Mutant Inhibitors for Treatment of Acute Myeloid Leukemia Treatment of isocitrate dehydrogenase 1 (IDH1) mutant primary acute myeloid leukemia cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. [Nat Chem Biol] Abstract A PI3K p110β-Rac Signaling Loop Mediates Pten-Loss-Induced Perturbation of Hematopoiesis and Leukemogenesis Scientists showed that when they delete phosphatase and tensin homolog (PTEN) in hematopoietic stem cells (HSCs) using the Mx1-Cre system, p110β ablation prevents myeloproliferative neoplasia, improves HSC function and suppresses leukemia initiation. [Nat Commun] Full Article Replication Stress Caused by Low MCM Expression Limits Fetal Erythropoiesis and Hematopoietic Stem Cell Functionality Investigators showed, using a mouse strain with hypomorphic expression of the origin licensing factor mini-chromosome maintenance (MCM)3 that limiting origin licensing in vivo affects the functionality of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. [Nat Commun] Full Article Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia Researchers report that hematopoietic cells differentiated from human induced pluripotent stem cells harboring Noonan syndrome/juvenile myelomonocytic leukemia (JMML)-causing PTPN11 mutations recapitulated JMML features. [Cell Rep] Full Article | Graphical Abstract | Press Release Co-Administration of the MTORC1/TORC2 Inhibitor INK128 and the Bcl-2/Bcl-XL Antagonist ABT-737 Kills Human Myeloid Leukemia Cells through Mcl-1 Down-Regulation and AKT Inactivation INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.g., FLT3, IDH2, NPM1, and Kras, while exerting minimal toxicity toward normal hematopoietic CD34+ cells. [Haematologica] Abstract All-trans Retinoic Acid Arrests Cell Cycle in Leukemic Bone Marrow Stromal Cells by Increasing Intercellular Communication through Connexin 43-Mediated Gap Junction Investigators evaluated the potential effects of all-trans retinoic acid (ATRA) on cell cycle, proliferation, and apoptosis of leukemic bone marrow stromal cells. Effects of ATRA on connexin 43 expression and gap junctional intercellular communication were also examined. [J Hematol Oncol] Full Article CLINICAL RESEARCH Influence of Differently Licensed KIR2DL1-Positive Natural Killer Cells in Transplant Recipients with Acute Leukemia: A Japanese National Registry Study Researchers analyzed 3866 recipients in the Japan national registry who underwent their first allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia or acute lymphoblastic leukemia from HLA-A, -B and -DRB1 allele-genomatched unrelated donors. [Biol Blood Marrow Transplant] Abstract Variable Eculizumab Clearance Requires Pharmacodynamic Monitoring to Optimize Therapy for Thrombotic Microangiopathy after Hematopoietic Stem Cell Transplantation Investigators examined the pharmacokinetics and pharmacodynamics of eculizumab in children and young adult hematopoietic stem cell transplant recipients with thrombotic microangiopathy and activated complement to determine drug dosing requirements for future efficacy trials. [Biol Blood Marrow Transplant] Abstract | Graphical Abstract |