Hematopoiesis News Volume 4.13 | Apr 9 2013

LABORATORY RESEARCH

Diverse and Heritable Lineage Imprinting of Early Hematopoietic Progenitors
Researchers used a new quantitative version of ‘cellular barcoding’ to trace the in vivo fate of hundreds of lymphoid-primed multipotent progenitors (LMPPs) and hematopoietic stem cells at the single-cell level. These data demonstrate that LMPPs are highly heterogeneous in the cell types that they produce, separating into combinations of lymphoid-, myeloid- and dendritic-cell-biased producers. [Nature] Abstract

Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation
Investigators developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia cells in vitro. [Science] Abstract | Press Release

Satb1 Regulates the Self-Renewal of Hematopoietic Stem Cells by Promoting Quiescence and Repressing Differentiation Commitment
Scientists identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of hematopoietic stem cell (HSC) fate. HSCs lacking Satb1 had defective self-renewal, were less quiescent and showed accelerated lineage commitment, which resulted in progressive depletion of functional HSCs. [Nat Immunol] Abstract

CD41 Expression Marks Myeloid Biased Adult Hematopoietic Stem Cells and Increases with Age
The authors showed that platelet integrin CD41, currently thought to only transiently mark fetal hematopoietic stem cells (HSCs), is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. [Blood] Abstract

Developmental Timing of Mutations Revealed by Whole-Genome Sequencing of Twins with Acute Lymphoblastic Leukemia
Researchers sequenced the whole genomes of leukemic cells from two twin pairs with acute lymphoblastic leukemia (ALL) to comprehensively characterize acquired somatic mutations in ALL, elucidating the developmental timing of all genetic lesions. [Proc Natl Acad Sci USA] Abstract

A Role for Reactive Oxygen Species in JAK2^V617F Myeloproliferative Neoplasm Progression
The authors showed that JAK2^V617F induces the accumulation of reactive oxygen species in the hematopoietic stem cell compartment of a knock-in mouse model and in patients with JAK2^V617F myeloproliferative neoplasms. [Leukemia] Abstract

TTC5 Is Required to Prevent Apoptosis of Acute Myeloid Leukemia Stem Cells
Using a screening strategy, researchers identified the tetratricopeptide repeat motif protein, Tetratricopeptide repeat domain 5 (TTC5) as required for the survival of human acute myeloid leukemia cells. [Cell Death Dis] Full Article

C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity
Testing >20 human lymphoma and leukemia B cell lines, researchers found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. [Cell Rep] Abstract | Graphical Abstract | Press Release

CLINICAL RESEARCH

Allogeneic Hematopoietic Cell Transplantation in First Remission Abrogates Poor Outcomes Associated with High-Risk Pediatric Acute Myeloid Leukemia
Researchers investigated whether allogeneic hematopoietic cell transplantation with best available donor in first remission would abrogate the poor outcomes associated with high-risk acute myeloid leukemia in chemotherapy treated children and young adults. [Biol Blood Marrow Transplant] Abstract

CMV Reactivation Is Associated with a Lower Incidence of Relapse after Allo-SCT for CML
Investigators studied the relationship of CMV reactivation with leukemic relapse in 110 patients with CML receiving HLA-identical sibling SCT. [Bone Marrow Transplant] Abstract

An Evolutionary Perspective on Chronic Myelomonocytic Leukemia
Chronic myelomonocytic leukemia shares with other myeloid diseases a number of somatic gene mutations. These mutations can now be integrated within the framework of evolution theory to address the mechanisms of the disease. This review discusses the various models of disease emergence and progression and how this recent knowledge could drive rational therapeutic strategies. [Leukemia] Abstract

PML-Mediated Signaling and Its Role in Cancer Stem Cells
The authors summarized and discussed the promyelocytic leukemia (PML)-mediated signaling pathways in cancers and their potential roles in regulating cancer stem cells. [Oncogene] Abstract

Visit our reviews page to see a complete list of reviews in the hematopoietic research field.

Immunotherapy Showed Promising Antileukemia Activity in Pediatric Patients
Researchers using patients’ own immune cells in an immunotherapy approach called “anti-CD19 chimeric antigen receptor T-cell therapy,” achieved responses in children whose acute lymphocytic leukemia had returned after a bone marrow transplant, according to preliminary results. [Press release from the American Association for Cancer Research (AACR) discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

More Accurate Markers Identified for Detecting Response to Epigenetic Drugs for Myelodysplastic Syndromes
Researchers have identified and validated two DNA methylation markers that could help physicians to more accurately determine a patient’s response to epigenetic drugs for treatment of myelodysplastic syndromes. [Press release from AACR discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

Phase II Ibrutinib Monotherapy Study Shows CLL Patients Achieved Rapid and Sustainable Disease Control Irrespective of Age or High Risk Prognostic Factor
Pharmacyclics, Inc. announced results from a Phase II trial of the investigational oral agent ibrutinib which demonstrated rapid and sustained disease control as a monotherapy in untreated, relapsed and refractory chronic lymphocytic leukemia (CLL) patients, irrespective of characteristics that predict poor outcomes to chemoimmunotherapy. [Press release from Pharmacyclics, Inc. discussing research presented at the AACR Annual Meeting 2013, Washington] Press Release

ASH Awards First Bridge Grants to Sustain Critical Hematology Research During Current Period of Funding Restrictions
The American Society of Hematology (ASH) announced the first recipients of the ASH Bridge Grants, a new award program designed to help hematologists continue their critical blood disease research amid severe funding reductions for the National Institutes of Health. [American Society of Hematology] Press Release

ERYTECH Pharma Receives FDA IND Clearance to Initiate a Clinical Study in Acute Lymphoblastic Leukemia in the U.S.
ERYTECH Pharma SA announced that it has received clearance of its Investigational New Drug (IND) Application from the United States Food and Drug Administration (FDA) to initiate a Phase I clinical trial of its product ERYASP®, L-asparaginase loaded erythrocytes, in patients 40 years or older with newly diagnosed Acute Lymphoblastic Leukemia. [ERYTECH Pharma SA] Press Release

Pharmacyclics Announces Third Breakthrough Therapy Designation for Ibrutinib from the U.S. Food and Drug Administration
Pharmacyclics, Inc. announced that the U.S. Food and Drug Administration has granted an additional Breakthrough Therapy Designation for the investigational oral agent ibrutinib as monotherapy for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma patients with deletion of the short arm of chromosome 17. [Pharmacyclics, Inc.] Press Release

Cord Blood Bank in Hong Kong Receives FACT Accreditation, Reflects High Quality Standards for Cord Blood Banking and Unit Administration
The Foundation for the Accreditation of Cellular Therapy (FACT) has accredited its first cord blood bank in Hong Kong. FACT accreditation demonstrates commitment to promote quality medical practices, laboratory processes, and banking to achieve consistent production of high quality placental and umbilical cord blood units for administration. The Hong Kong Red Cross Catherine Chow Cord Blood Bank, directed by Dr. Che Kit Lin, received accreditation and is accredited for unrelated donations. [Foundation for the Accreditation of Cellular Therapy] Press Release

China Cord Blood Corporation Received AABB Accreditation
China Cord Blood Corporation announced that the cord blood bank operated by its Beijing subsidiary has been granted the AABB Accreditation, as a certification of its quality excellence of providing cord blood processing and storage services. [China Cord Blood Corporation] Press Release

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NEW The Jackson Laboratory: Modeling Human Malignancy with Patient-Derived Xenograft Cancer Models
April 18, 1:00PM (ET in US)
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NEW Gordon Research Conferences: Cell Growth & Proliferation
June 22-23, 2013
West Dover, United States

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

Postdoctoral Position – Stem Cell Research (University of Washington)

Postdoctoral Position – Bioinformatics and Stem Cell Biology (University of Texas at Houston)

Postdoctoral Position – Stem Cells and Cancer (Tsinghua University)

Cord Blood Laboratory Manager (Puget Sound Blood Center)

Postdoctoral Positions (Cancer Science Institute of Singapore)

Postdoctoral Positions – Cell Death Signaling & Cancer (Goethe Universität Frankfurt, Institute for Experimental Cancer Research in Pediatrics)

Postdoctoral Research Associate (Washington State University)

Postdoctoral Position – Hematopoietic Stem Cell Biology (Institut Pasteur, Labex Revive)

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