Hematopoiesis News Volume 7.14 | Apr 12 2016

Dnmt3a Haploinsufficiency Transforms Flt3-ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully-Penetrant Acute Myeloid Leukemia
Investigators demonstrated that mice with Flt3-internal-tandem duplication (Flt3-ITD) and inducible deletion of Dnmt3a spontaneously develop a rapidly-lethal, completely-penetrant, and transplantable acute myeloid leukemia of normal karyotype. [Cancer Discov] Abstract | Full Article

Adult Hematopoietic Stem Cells Lacking Hif-1α Self-Renew Normally
Researchers demonstrated that inducible acute deletion of Hif-1α has no impact on hematopoietic stem cell survival. [Blood] Abstract

Lineage Specific STAT5 Target Gene Activation in Hematopoietic Progenitor Cells Predicts the FLT3⁺-Mediated Leukemic Phenotype
Researchers report that the presence of STAT5 is critical for the development of a myeloproliferative disease by Fms-like-tyrosinkinase (FLT3) 3-internal duplication of the juxtamembranous domain in mice. [Leukemia] Abstract

Insight into GATA1 Transcriptional Activity through Interrogation of Cis Elements Disrupted in Human Erythroid Disorders
The authors used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. [Proc Natl Acad Sci USA] Full Article

Transformation of Human CD34⁺ Hematopoietic Progenitor Cells with DEK-NUP214 Induces AML in an Immunocompromised Mouse Model
Investigators described the development of a human cell acute myeloid leukemia (AML), generated in CD34⁺ human hematopoietic progenitor cells xenografted into immunocompromised mice that express human myeloid cell growth factors. [Oncogene] Abstract

Elimination of Chronic Lymphocytic Leukemia Cells in Stromal Microenvironment by Targeting CPT with an Antiangina Drug Perhexiline
The authors discovered that perhexiline, an antiangina agent that inhibits carnitine palmitoyltransferases (CPT), was highly effective in killing chronic lymphocytic leukemia cells in stromal microenvironment at clinically achievable concentrations. [Oncogene] Abstract

Direct Bone Marrow HSC Transplantation Enhances Local Engraftment at the Expense of Systemic Engraftment in NSG Mice
Relevant combinations of human umbilical cord blood-derived CD34⁺ cells and bone marrow-derived mesenchymal stem/stromal cells were transplanted into NOD/SCID gamma (NSG) mice using either intravenous or intrafemoral routes. [Sci Rep] Full Article

Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1 Transcription Factors
By induced deletion of Tcf1 and Lef1 in pre-established CML, scientists further demonstrated an intrinsic requirement for these factors in leukemic stem cells self-renewal. [J Biol Chem] Abstract | Full Article

CLINICAL RESEARCH

Highly Favorable Outcome in BRCA-Mutated Metastatic Breast Cancer Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
Researchers hypothesized a better outcome for BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation versus unaffected BRCA or patients without documented BRCA mutation. [Bone Marrow Transplant] Abstract

Lymphodepleting Chemotherapy with Donor Lymphocyte Infusion Post-Allogeneic HCT for Hematological Malignancies Is Associated with Severe, but Therapy-Responsive aGvHD
The authors analyzed the incidence of acute GvHD (aGvHD) in patients treated with donor lymphocyte infusion (DLI). They observed frequent, yet therapy-responsive aGvHD following DLI. GI GvHD in particular is a significant risk when giving chemotherapy prior to DLI. [Bone Marrow Transplant] Abstract

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Method for Earlier Detection of Leukemia Wins $300,000 Grant
A unique pitch competition hosted by the MIT Koch Institute for Integrative Cancer Research awarded a team of researchers $300,000 to further develop — and potentially commercialize — a diagnostic platform that promises to catch leukemic cells in blood tests at very early stages of the disease. [Massachusetts Institute of Technology] Press Release

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Visit our events page to see a complete list of events in the hematopoiesis community.

NEW Engineering Project Lead (Cytonome)

Scientist – Hematology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Hematopoietic and Leukemic Stem Cells (The Francis Crick Institute)

Postdoctoral Scientist – Hematological Malignancies (Max Delbruck Center for Molecular Medicine in the Helmholtz Association)

Postdoctoral Fellow – Molecular and Cellular Basis of Hematopoiesis (University of Cincinnati)

Postdoctoral Research Associate – Blood Stem cell Microenvironment (University of Illinois)

Associate Scientist – Hematopoietic Stem Cell Biology (Editas Medicine)

Research Associate – Hematopoietic Stem Cell Biology (Editas Medicine)

Postdoctoral Fellow Positions – Leukemogenesis (The University of Alabama)

Postdoctoral Fellow – Hematology/Oncology (Boston Children’s Hospital)

Postdoctoral Fellow – Cancer Biology (National University of Singapore)

Assistant/Associate/Full Member Faculty – Myeloid Malignancies (Fred Hutchinson Cancer Research Center)

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