Hematopoiesis News 8.07 February 21, 2017 | |
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TOP STORYCpG Island Hypermethylation Mediated by DNMT3A Is a Consequence of AML Progression To understand the contribution of DNMT3A-dependent methylation to leukemogenesis, investigators performed whole-genome bisulfite sequencing of primary leukemic and non-leukemic cells in patients with or without DNMT3AR882 mutations. Non-leukemic hematopoietic cells with DNMT3AR882H displayed focal methylation loss, suggesting that hypomethylation antedates acute myeloid leukemia. [Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Prospective Identification of Hematopoietic Lineage Choice by Deep Learning Scientists present a deep neural network that prospectively predicts lineage choice in differentiating primary hematopoietic progenitors using image patches from brightfield microscopy and cellular movement. Surprisingly, lineage choice can be detected up to three generations before conventional molecular markers are observable. [Nat Methods] Abstract | Press Release Researchers derived a collection of induced pluripotent stem cell lines capturing a range of disease stages encompassing preleukemia, low-risk myelodysplastic syndrome (MDS), high-risk MDS, and secondary acute myeloid leukemia. Upon their differentiation, they found hematopoietic phenotypes of graded severity and/or stage specificity that together delineate a phenotypic roadmap of disease progression culminating in serially transplantable leukemia. [Cell Stem Cell] Abstract | Graphical Abstract Differential Cytokine Contributions of Perivascular Hematopoietic Stem Cell Niches Investigators showed that the effects of cytokines regulating hematopoietic stem cells (HSCs) functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor from all perivascular cells marked by nestin-GFP dramatically depleted bone marrow (BM) HSCs. Selective Cxcl12 deletion from arteriolar NG2+ cells, but not from sinusoidal LepR+ cells, caused HSC reductions and altered HSC localization in BM. [Nat Cell Biol] Abstract Novel lysine-specific demethylase 1 (LSD1) inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and acute myeloid leukemia oncogenic programs, and commonly upregulated 62 genes in several leukemia cells. [Leukemia] Abstract Fumarate Hydratase Is a Critical Metabolic Regulator of Hematopoietic Stem Cell Functions Researchers investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion caused lethal fetal liver hematopoietic defects and hematopoietic stem cell failure. [J Exp Med] Full Article Long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Scientists provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells, which actively suppressed antitumor immune responses. [Oncogene] Abstract To screen the Notch1-related genes that regulate differentiation fate of K562 and HEL cells, the expression of transient receptor potential ankyrin 1 (TRPA1) was induced by Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor. N1IC and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1) bound to TRPA1 promoter region to regulate transcription in K562 cells. [Sci Rep] Full Article PTC596 induced apoptosis in a p53-independent manner. PTC596 induced apoptosis along with the reduction of MCL-1 and phosphorylated AKT in patient-derived CD34+CD38low/− stem/progenitor cells. Mouse xenograft models demonstrated in vivo anti-leukemia activity of PTC596, which inhibited leukemia cell growth in vivo while sparing normal hematopoietic cells. [Blood Cancer J] Full Article CLINICAL RESEARCHLong-Term Outcome of Hematopoietic Stem Cell Transplantation for IL2RG/JAK3 SCID-: A Cohort Report Scientists performed longitudinal analyses of CD3+, CD4+ naïve T-lymphocyte, CD19+ and natural killer cell numbers from pre-transplant until 15 years post-transplant. 31/43 patients survived. Median age at last follow-up was 10 years. 21 had persistent medical issues, mainly on-going immunoglobulin replacement, cutaneous viral warts, short stature, limb lymphedema and bronchiectasis. [Blood] Abstract The authors retrospectively studied outcomes of transplantation for cases of primary refractory acute lymphoblastic leukemia (PREF ALL) reported to European Society for Blood and Marrow Transplantation registry. Eligibility criteria for the current analysis included adult patients who underwent their first hematopoietic cell transplantation (HCT) for PREF ALL between 2000 and 2012. PREF disease was defined as the failure to achieve a morphological complete remission after greater than two courses of induction chemotherapy. [Cancer] Abstract | |
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REVIEWSRegulation of Inflammation- and Infection-Driven Hematopoiesis During severe systemic bacterial infection, myeloid cell turnover is dramatically increased due to their unique modus operandi in combating invading pathogens involving release of lytic enzymes and neutrophil extracellular traps. Consequently, steady-state hematopoiesis is switched to emergency hematopoiesis by launching a unique hematopoietic response program that is aimed at greatly increasing myeloid cell output to meet the higher demand. The authors discuss the well-established as well as recently emerging concepts around the regulation of this fundamental process. [Trends Immunol] Abstract Non-Apoptotic Functions of Caspases in Myeloid Cell Differentiation Subtle caspase activation is associated with the differentiation of several myeloid lineages. A tightly orchestrated dance between caspase-3 activation and the chaperone HSP70 that migrates to the nucleus to protect the master regulator GATA-1 from cleavage transiently occurs in basophilic erythroblasts and may prepare nucleus and organelle expel that occurs at the terminal phase of erythroid differentiation. [Cell Death Differ] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
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INDUSTRY NEWSPfizer Inc. announced that a Biologics License Application for inotuzumab ozogamicin has been accepted for filing and granted Priority Review by the U.S. Food and Drug Administration. Inotuzumab ozogamicin is being evaluated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. [Pfizer Inc.] Press Release Immune Pharmaceuticals Inc. announced that it will be launching REMAINâ„¢, an international Overall Survival clinical study with the combination of Ceplene®, the company’s flagship product for Acute Myeloid Leukemia remission maintenance and relapse prevention, and low dose Proleukin®. [Immune Pharmaceuticals Inc.] Press Release The Scripps Research Institute Announces New Board Members and Chairman of the Board The Scripps Research Institute announced the appointment of nine new members to its Board of Directors, including John D. Diekman, who will serve as chairman of the board. Diekman replaces Richard A. Gephardt, who is retiring from the board after seven years of service. [The Scripps Research Institute] Press Release | |
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POLICY NEWSDelay in Hiring Science Advisers Intensifies Brexit Worries Policy experts want scientists to be at the table when government decides on environmental protection and membership of international collaborations. [Nature News] Editorial Why the CRISPR Patent Verdict Isn’t the End of the Story The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. But the fight for patent rights to CRISPR technology is by no means over. [Nature News] Editorial
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EVENTSNEW Stem Cells and Regenerative Medicine 2nd International Congress NEW Stem Cell Summit Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine) Principal Scientist – Translational Development, Myeloid Disease Strategy (Celgene Corporation) Senior Scientist – Translational and Diagnostic Informatics (Celgene Corporation) Scientist – Regulatory Support (Cook MyoSite, Inc.) Postdoctoral Position – Leukemia Research (Department of Biomedicine, University Hospital Basel) Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame) Research Specialist – Metabolomics Methods to Stem Cell Metabolism (Howard Hughes Medical Institute) Principal Scientist – Translational Development (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Postdoctoral Fellow – Hematopoietic Development and Homeostasis (Harvard Medical School, BIDMC) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Hematopoiesis News Volume 8.07 | Feb 21 2017