Hematopoiesis News Volume 4.20 | May 28 2013

LABORATORY RESEARCH

RIP1-Driven Autoinflammation Targets IL-1α Independently of Inflammasomes and RIP3
Mice homozygous for the Tyr208Asn amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6^spin mice) spontaneously develop a severe inflammatory syndrome that resembles neutrophilic dermatosis in humans and is characterized by persistent footpad swelling and suppurative inflammation. Researchers report that receptor-interacting protein 1 (RIP1)-regulated interleukin (IL)-1α production by hematopoietic cells critically mediates chronic inflammatory disease in Ptpn6^spin mice, whereas inflammasome signaling and IL-1β-mediated events are dispensable. [Nature] Abstract

The Transcriptional Architecture of Early Human Hematopoiesis Identifies Multilevel Control of Lymphoid Commitment
Understanding how differentiation programs originate from the gene-expression ‘landscape’ of hematopoietic stem cells (HSCs) is crucial for the development of new clinical therapies. Scientists mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSCs and eight early progenitor populations. [Nat Immunol] Abstract

Deficiency of Lipid Phosphatase SHIP Enables Long-Term Reconstitution of Hematopoietic Inductive Bone Marrow Microenvironment
Investigators showed that a deficiency of SH2-containing inositol-5′-phosphatase-1 (SHIP) in a nonhematopoietic host microenvironment enables its functional reconstitution by wild-type donor cells. This microenvironment reconstitution normalizes hematopoiesis in peripheral blood and bone marrow and alleviates pathology of spleen and lung in the SHIP-deficient recipients. [Dev Cell]
Abstract | Full Article | Press Release

WT1 Regulates Murine Hematopoiesis via Maintenance of VEGF Isoform Ratio
The authors showed that Wilms’ tumor suppressor 1 (WT1)-deficient mouse embryonic stem cells exhibit reduced hematopoietic potential caused by Vegf-a dependent apoptosis of hematopoietic progenitor cells associated with overproduction of the Vegf-a₁₂₀ isoform. [Blood] Abstract

Expression Levels of Endoglin Distinctively Identify Hematopoietic and Endothelial Progeny at Different Stages of Yolk Sac Hematopoiesis
Investigators evaluated the function of endoglin in hematopoiesis as development progresses past E7.5, and found that the hematopoietic and endothelial progenitors can be distinguished by the levels of endoglin in E9.5 yolk sacs. [Stem Cells] Abstract

HOX-Mediated LMO2 Expression in Embryonic Mesoderm Is Recapitulated in Acute Leukemias
Given the importance of both Lim Domain Only 2 (LMO2) and HOX genes in acute leukemias, researchers demonstrated that the regulatory hierarchy of HOX control of LMO2 is activated in leukemia mouse models as well as in patient samples. Moreover, Lmo2 knock-down impaired the growth of leukemic cells, and high LMO2 expression at diagnosis correlated with poor survival in cytogenetically normal AML patients. [Oncogene] Full Article

Revision of the Human Hematopoietic Tree: Granulocyte Subtypes Derive from Distinct Hematopoietic Lineages
Investigators showed that eosinophilic and basophilic granulocytes as well as erythrocytes and megakaryocytes derive from a common erythro-myeloid progenitor, whereas neutrophilic granulocytes arise independently within a lympho-myeloid branch with long-term progenitor function. [Cell Rep]
Abstract | Full Article | Graphical Abstract

MicroRNA-146a Acts as a Guardian of the Quality and Longevity of Hematopoietic Stem Cells in Mice
Researchers identified microRNA-146a to be a critical regulator of hematopoietic stem cell homeostasis during chronic inflammation in mice and provided a molecular connection between chronic inflammation and the development of bone marrow failure and myeloproliferative neoplasms. [eLife]
Full Article | Press Release

CLINICAL RESEARCH

Randomized Trial Comparing Liposomal Daunorubicin with Idarubicin in Induction for Pediatric Acute Myeloid Leukemia: Results from Study AML-BFM 2004
Outcome of adult and pediatric patients with AML improved significantly by intensification of induction treatment. To further intensify anthracycline-dosage without increasing cardiotoxicity, scientists compared the potentially less cardiotoxic liposomal daunorubicin at a higher than equivalent dose (80mg/m²/day/x3) to idarubicin (12mg/m²/day/x3) during induction. [Blood] Abstract

Hemorrhagic Cystitis in a Cohort of Pediatric Transplants: Incidence, Treatment, Outcome and Risk Factors
Hemorrhagic cystitis can be a severe complication in HSCT. In order to identify risk factors and etiology and to improve treatment, a number of factors were analyzed retrospectively in a cohort of 74 consecutive pediatric HSCTs. [Biol Blood Marrow Transplant] Abstract

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

Using One Grant to Tackle Two Diseases
Scientists thought hematopoietic stem cells stayed in the bone marrow but recent research has revealed that they, too, travel to the problem site: to the heart if a heart attack is in progress, or to the brain in the case of a stroke. Why these cells leave the bone marrow, how they know where to go, and what they do when they reach their target is what Jennifer Gillette, PhD, will use her $300,000 American Heart Association grant to study over the next four years. [The University of New Mexico Cancer Center] Press Release

Lyda Hill Commits $50 Million to Moon Shots Program
Lyda Hill, of Dallas, has pledged $50 million to The University of Texas MD Anderson Cancer Center’s Moon Shots Program, an unprecedented, comprehensive assault on cancer announced in September 2012. [The University of Texas MD Anderson Cancer Center] Press Release

Stem Cell Agency Awards More than $42 Million in New Research and Leadership Funding
California’s position as a global leader in stem cell research has been strengthened by the awarding of $36 million in funds to attract six world-class scientists to the state, and more than $6 million to create a partnership with Sangamo BioSciences to develop a therapy for beta-thalassemia. [California Institute for Regenerative Medicine] Press Release

Maryland Stem Cell Research Commission Funds 31 New Research Proposals in FY 2013
The Maryland Stem Cell Research Commission has completed its review of the 171 applications received in response to its FY 2013 Requests for Applications. The board of directors of the Maryland Technology Development Corporation approved the Commission’s recommendation to fund 31 new proposals with the Maryland Stem Cell Research Fund’s $10.4 million FY2013 budget. [Maryland Stem Cell Research Fund] Press Release

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