Volume 6.46 | Nov 24

Hematopoiesis News 6.46 November 24, 2015
Hematopoiesis News
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Synthetic Lethal Targeting of Oncogenic Transcription Factors in Acute Leukemia by PARP Inhibitors
Researchers demonstrated that acute myeloid leukemia driven by repressive transcription factors, including AML1-ETO and PML-RARα fusion oncoproteins are extremely sensitive to poly (ADP-ribose) polymerase (PARP) inhibition, in part owing to their suppressed expression of key homologous recombination-associated genes and their compromised DNA-damage response. [Nat Med] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Insulin-InsR Signaling Drives Multipotent Progenitor Differentiation toward Lymphoid Lineages
The authors showed that insulin-insulin receptor (InsR) signaling is required for lineage commitment of multipotent progenitors (MPPs). Deletion of Insr in murine bone marrow causes skewed differentiation of MPPs to myeloid cells. [J Exp Med] Abstract

AF4 Uses the SL1 Components of RNAP1 Machinery to Initiate MLL Fusion- and AEP-Dependent Transcription
Scientists showed that AEP (AF4 family/ENL family/P-TEFb) and MLL–AEP fusion proteins activate transcription through selectivity factor 1 (SL1). [Nat Commun] Full Article

Hoxa Cluster Genes Determine the Proliferative Activity of Adult Mouse Hematopoietic Stem and Progenitor Cells
Investigators showed that conditional homozygous deletion of the Hoxa cluster results in marked reduction of adult hematopoietic stem and progenitor cell activity, both in vitro and in vivo. [Blood] Abstract

Cross-Talk between PRMT1-Mediated Methylation and Ubiquitylation on RBM15 Controls RNA Splicing
Scientists demonstrated that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578 leading to its degradation via ubiquitylation by an E3 ligase. Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by downregulation of RBM15 protein level. [eLife] Abstract | Full Article

Combined Loss of Tet1 and Tet2 Promotes B Cell, but Not Myeloid Malignancies, in Mice
Tet1/2 double-knockout (DKO) and Tet2−/− HSC/HPCs showed overlapping and unique 5hmC and 5mC profiles. DKO mice exhibited strikingly decreased incidence and delayed onset of myeloid malignancies in comparison to Tet2−/−mice and in contrast develop lethal B cell malignancies. [Cell Rep] Full Article | Graphical Abstract

Drosophila Rabex-5 Restricts Notch Activity in Hematopoietic Cells and Maintains Hematopoietic Homeostasis
Investigators report that loss of the gene Rabex-5 in Drosophila causes several hematopoietic abnormalities including blood cell overproliferation, increased size of the hematopoietic organ, lamellocyte differentiation, and melanotic mass formation. [J Cell Sci] Abstract | Full Article

Systematic Analysis of Hematopoietic Gene Expression Profiles for Prognostic Prediction in Acute Myeloid Leukemia
Researchers investigated the roles of the canonical and non-canonical Wnt pathway in hematopoiesis and thymopoiesis. [Cell Death Dis] Full Article


Peripheral Blood Stem Cell Graft Compared to Bone Marrow after Reduced Intensity Conditioning Regimens for Acute Leukemia – A Report from the ALWP of the EBMT
The authors hypothesized that the use of bone-marrow graft might decrease the risk of graft-versus-host-disease compared to peripheral-blood after reduced-intensity-conditioning regimens without compromising graft-versus-leukemia effects. [Haematologica] Abstract | Full Article

Long-Term Outcomes of Fludarabine, Melphalan and Antithymocyte Globulin as Reduced-Intensity Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Primary Immunodeficiency Disorders: A Prospective Single Center Study
Forty-five children affected by primary immunodeficiency disorder with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation. Eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. [Bone Marrow Transplant] Abstract

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Allogeneic Transplantation for CML in the TKI Era: Striking the Right Balance
The majority of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) achieve excellent responses with sustained treatment; however, for an almost equal number of patients, an adequate response cannot be achieved with any of the currently available TKIs. For those patients who fail to respond adequately to TKIs, hematopoietic stem-cell transplantation offers the best prospect of long-term survival. [Nat Rev Clin Oncol] Abstract

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European Commission Approves Amgen’s BLINCYTO® (Blinatumomab) for the Treatment of Adults with Philadelphia Chromosome-Negative Relapsed or Refractory B-Precursor Acute Lymphoblastic Leukemia
Amgen announced that the European Commission has granted conditional marketing authorization for BLINCYTO® for the treatment of adults with Philadelphia chromosome-negative relapsed or refractory B-precursor acute lymphoblastic leukemia. [Amgen Inc.] Press Release

Oxis Biotech – University of Minnesota Masonic Cancer Center Receive FDA Allowance to Proceed with OXS-1550 (DT2219ARL) Phase I/Phase II Clinical Trial
Oxis Biotech, Inc. announced its collaborators at the University of Minnesota Masonic Cancer Center received notification from the U.S. Food and Drug Administration (FDA) that they can proceed with their planned combination Phase I/Phase II clinical trial for OXS-1550. Oxis holds worldwide exclusive rights to develop and commercialize OXS-1550, a novel therapy for the treatment of leukemia and lymphoma. [Oxis Biotech, Inc.] Press Release

MD Anderson Receives $22.2 Million in CPRIT Research Funding
The University of Texas MD Anderson Cancer Center was awarded more than $22 million in research grants from the Cancer Prevention and Research Institute of Texas (CPRIT). MD Anderson CPRIT awards included $14.8 million for research, $6 million in recruitment funding and $1.4 million for evidence-based cancer prevention services. [The University of Texas MD Anderson Cancer Center] Press Release

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NEW Cancer as an Evolving and Systemic Disease
March 12-15, 2016
New York City, United States

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

Team Leader/Professor/Associate Professor – Regenerative Medicine (Ji Nan University)

Postdoctoral Researcher – Cardiovascular/Hematopoietic Development (Kumamoto University)

Postdoctoral Fellow – Leukemia Research (City of Hope)

Postdoctoral Position – Stem Cells and Leukemia (Florida State University)

Assistant or Associate Professor – Cell and Regenerative Biology (University of Wisconsin, Madison)

Postdoctoral Research Fellow – Medicinal Chemistry for Cancer Drug Discovery (University of Michigan)

Research Technician – Stem Cell and Gene Therapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – iPSC Models of Hematologic Disorders (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Leukemia, Stem Cells and Development (Josep Carreras Leukemia Research Institute)

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