Hematopoiesis News Volume 7.06 | Feb 16 2016

Functional Screen Identifies Regulators of Murine Hematopoietic Stem Cell Repopulation
To discover novel regulators of hematopoietic stem and progenitor cell (HSPC) repopulation, scientists transplanted >1,300 mice with shRNA-transduced HSPCs within 24 hours of isolation and transduction to focus on detecting genes regulating repopulation. They identified 17 regulators of HSPC repopulation. [J Exp Med] Abstract | Press Release

GFI1 as a Novel Prognostic and Therapeutic Factor for AML/MDS
Scientists showed that acute myeloid leukemia (AML) development induced by onco-fusion proteins such as MLL-AF9 or NUP98-HOXD13 is accelerated in mice with low human GFI1 expression. [Leukemia] Abstract

Endogenous Dendritic Cells from the Tumor Microenvironment Support T-ALL Growth via IGF1R Activation
Systematic evaluation of the functional capacity of tumor-associated stromal cells revealed that myeloid cells, primarily dendritic cells, are necessary and sufficient to support T-cell acute lymphoblastic leukemia (T-ALL) survival ex vivo. [Proc Natl Acad Sci USA] Abstract | Press Release

Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression
Transcriptomic analyses showed that monocytes/macrophages and leukemic cells cross talk during chronic lymphocytic leukemia (CLL) progression. Macrophage depletion impaired CLL engraftment, drastically reduced leukemic growth, and favorably impacted mouse survival. [Cell Rep] Full Article | Graphical Abstract

Jam-A Is Highly Expressed on Human Hematopoietic Repopulating Cells and Associates with the Key Hematopoietic Chemokine Receptor cxcr4
Two junctional adhesion molecule family proteins, JAM-B and JAM-C, are reported to mediate hematopoietic stem/progenitor cell-stromal cell interactions, which in turn regulate CXCL12 production by mesenchymal stromal cells. Here, scientists demonstrated that another JAM family member, JAM-A, is most highly expressed on human hematopoietic stem cells with in vivo repopulating activity. [Stem Cells] Abstract

ATF4 Induction through an Atypical Integrated Stress Response to ONC201 Triggers p53-Independent Apoptosis in Hematological Malignancies
Researchers found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma and acute myeloid leukemia (AML) samples from patients. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. [Sci Signal] Abstract | Press Release

CLINICAL RESEARCH

Hematopoietic Stem Cell Transplantation for Homozygous β-Thalassemia and β-Thalassemia/Hemoglobin E Patients from Haploidentical Donors
Investigators explored the use of a mismatched-related (‘haplo- ’) donor. Thirty-one patients underwent haplo-stem cell transplantation. [Bone Marrow Transplant] Abstract

Efficacy of Cisplatin-Based Immunochemotherapy plus AlloSCT in High-Risk Chronic Lymphocytic Leukemia: Final Results of a Prospective Multicenter Phase II HOVON Study
Scientists prospectively assessed outcome after cisplatin-containing immune-chemotherapy followed by allogeneic stem cell transplantation in 46 patients being refractory to or relapsed (R/R) <1 year after fludarabine or <2 years after fludarabine-based immunochemotherapy or R/R with del(17p). [Bone Marrow Transplant] Abstract

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Red or White? Healthy Humans Need Both
A Canadian investigation recently launched to the International Space Station will explore the effects of spaceflight on blood cells. [NASA/Johnson Space Center (EurekAlert!)] Press Release

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NEW Lead Scientist – Translational Therapy (NHS Blood and Transplant)

NEW PhD Position – Leukemogenesis and Treatment Resistance (Institute for Tumor Biology and Experimental Therapy)

Translational Research Scientist – Hematology/Oncology (University of Chicago)

Postdoctoral Associate – Epigenetic Regulation of Normal and Leukemic Stem Cells (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral Researcher – Pre-Leukemic Stem Cells in the Thymus (Ghent University)

Laboratory Technician – Molecular Biology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Scholarship – Cancer Biology (Lund University)

Postdoctoral Position – Epigenetics and RNA Splicing (National Cancer Institute)

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

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