Chemically Modified Guide RNAs Enhance CRISPR-Cas Genome Editing in Human Primary Cells The authors report that chemical alterations to synthesized single guide RNAs enhanced genome editing efficiency in human primary T cells and CD34+ hematopoietic stem and progenitor cells. [Nat Biotechnol] Abstract Aspp1 Preserves Hematopoietic Stem Cell Pool Integrity and Prevents Malignant Transformation Researchers showed that Aspp1 coordinated with p53 to maintain the genomic integrity of the hematopoietic stem cell (HSC) pool. Aspp1 is preferentially expressed in HSCs and restricts HSC pool size by attenuating self-renewal under steady-state conditions. [Cell Stem Cell] Abstract | Graphical Abstract Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions Scientists found that all multipotent progenitors are produced in parallel by hematopoietic stem cells, but with different kinetics and at variable levels depending on hematopoietic demands. [Cell Stem Cell] Abstract Plerixafor+G-CSF-Mobilized CD34+ Cells Represent an Optimal Graft Source for Thalassemia Gene Therapy CD34+ cells from 31 thalassemic patients mobilized with Hydroxyurea+G-CSF, G-CSF, Plerixafor or Plerixafor+G-CSF were transduced with the TNS9.3.55 β-globin lentivector and compared for transducibility and globin expression in vitro, as well as engraftment potential in a xenogeneic model after partial myeloablation. [Blood] Abstract FoxO1-Dependent Induction of Acute Myeloid Leukemia by Osteoblasts in Mice Scientists showed that Notch1 is the receptor mediating the leukemogenic properties of osteoblast-activated β-catenin in hematopoietic stem cells. [Leukemia] Abstract EphA2 Is a Therapy Target in EphA2-Positive Leukemias but Is Not Essential for Normal Hematopoiesis or Leukemia Investigators explored the role of EphA2 in hematopoiesis by analyzing wild type and EphA2 knockout mice. Mature, differentiated cells, progenitors and hematopoietic stem cells derived from knockout and control mice were analyzed and no significant abnormality was detected. These studies showed that EphA2 does not have an obligatory role in normal hematopoiesis. [PLoS One] Full Article Retrovirus-Mediated Expression of E2A-PBX1 Blocks Lymphoid Fate but Permits Retention of Myeloid Potential in Early Hematopoietic Progenitors Researchers elucidated the hematopoietic consequences of forced E2A-PBX1 expression in primary murine hematopoietic progenitors. They showed that introducing E2A-PBX1 into multipotent progenitors permitted the retention of myeloid potential but imposed a dense barrier to lymphoid development prior to the common lymphoid progenitor stage [PLoS One] Full Article CLINICAL RESEARCH Outcomes of Patients with Therapy-Related AML/Myelodysplastic Syndrome (T-AML/MDS) following Hematopoietic Cell Transplantation The authors studied outcomes of 65 consecutive patients with therapy-related AML/myelodyplastic (t-AML/MDS) syndrome who underwent allogeneic hematopoietic cell transplantation. Patients with t-AML/MDS had poor overall survival (OS). Unrelated donor is a significant risk factor for both higher NRM and decreased OS. [Bone Marrow Transplant] Abstract Second Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Aplastic Anemia The outcome of 55 children with severe aplastic anemia who received a second hematopoietic stem cell transplantation was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival and failure-free survival after the second transplantation were 82.9% and 81.2%, respectively. [Bone Marrow Transplant] Abstract Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) Overcomes Poor Prognosis of Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Researchers analyzed transplant outcomes among 147 patients with AML-MRC or AML-NOS who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution. There were no significant differences in the 2-year overall survival, cumulative incidence of relapse, and non-relapse mortality between the two groups. [Leuk Lymphoma] Abstract |