Hematopoiesis News 8.19 May 16, 2017 | |
| |
TOP STORYScientists developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. They applied this technique to analyze more than 2,000 cancer stem cells (SC) from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. [Nat Med] Abstract | Press Release | |
| |
PUBLICATIONS(Ranked by impact factor of the journal)Regulation of Mitochondrial Biogenesis in Erythropoiesis by mTORC1-Mediated Protein Translation Investigators compared the genome-scale proteomic and transcriptomic changes in human primary hematopoietic stem/progenitor cells and erythroid progenitors, and uncovered pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 were selectively regulated through protein translation during erythroid specification. [Nat Cell Biol] Abstract The Mitochondrial Respiratory Chain Is Essential for Hematopoietic Stem Cell Function The authors report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse hematopoietic stem cells (HSCs) allows them to proliferate but impairs their differentiation, resulting in anemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD+/NADH ratio. [Nat Cell Biol] Abstract Abundant and Equipotent Founder Cells Establish and Maintain Acute Lymphoblastic Leukemia Researchers used cellular barcoding as a fate mapping tool to track primograft acute lymphoblastic leukemia (ALL) blasts in vivo. Their results showed that high numbers of ALL founder cells contributed at similar frequencies to leukemic propagation over serial transplants, without any clear evidence of clonal succession. [Leukemia] Abstract | Full Article Scientists established a specific requirement for the P1-RUNX1C isoform in megakaryopoiesis, which cannot be entirely compensated for by RUNX1B overexpression. P1 knock-in megakaryocyte progenitors had reduced proliferative capacity and undergo increased cell death, resulting in thrombocytopenia. P1 knock-in pre-megakaryocyte/erythroid progenitors demonstrated an erythroid-specification bias, evident from increased erythroid colony-forming ability and decreased megakaryocyte output. [Blood] Abstract SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor Cells Using histone 2B-red fluorescent fusion protein label retention and cell-cycle reporter mice, investigators demonstrated that high Stem cell antigen 1 (SCA-1hi) expression identifies not only quiescent hematopoietic stem cells but quiescent cells on all hierarchical levels within the lineage−SCA-1+KIT+ population. Each transplanted SCA-1hi hematopoietic stem and progenitor cell population also displayed self-renewal potential superior to that of the respective SCA-1lo population. [Stem Cell Reports] Full Article | Graphical Abstract Researchers characterized the in vivo primary responses of dysregulated genes in acute promyelocytic leukemia (APL) cells treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) using a GFP-labeled APL model. Although induced granulocytic differentiation of APL cells was evident after ATRA or ATO administration, the expression of the majority of dysregulated genes in the c-Kit+ APL progenitors was not consistently corrected. [Cell Death Dis] Full Article PLSCR1/IP3R1/Ca2+ Axis Contributes to Differentiation of Primary AML Cells Induced by Wogonoside Investigators report that wogonoside promotes the expression of phospholipid scramblase 1 (PLSCR1) and enhances its nuclear translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter in acute myeloid leukemia (AML) patient-derived primary cells. Wogonoside activates IP3R1, in turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads to cell differentiation. [Cell Death Dis] Full Article ALOX5 Exhibits Anti-Tumor and Drug-Sensitizing Effects in MLL-Rearranged Leukemia The authors found that ALOX5 is especially down-regulated in MLL-rearranged acute myeloid leukemia (AML), via transcription repression mediated by Polycomb repressive complex 2. Colony forming/replating and bone marrow transplantation assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. [Sci Rep] Full Article Investigators established B cell derived induced pluripotent stem cells (BiPSC-A) in which activation-induced cytidine deaminase (AID) could be induced using the doxycycline-controlled. Both the parental BiPSC and BiPSC-A showed the capability of differentiating into hematopoietic progenitor cells based on confirmation of CD34 expression and colony-formation from CD34-positive cells. [Sci Rep] Full Article CLINICAL RESEARCHResearchers treated 42 primary refractory/hematological relapsed and 9 refractory minimal residual disease by flow cytometry B lymphoblastic leukemia (B-ALL) patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages initially ranged from 0.05 to 14 × 105/kg and eventually settled at 1 × 105/kg for the most recent 20 cases. [Leukemia] Abstract | |
| |
REVIEWSWhy Are Hematopoietic Stem Cells So ‘Sexy’?—on a Search for Developmental Explanation Sex hormone receptors are also expressed by leukemic cell lines and blasts. The author discusses the emerging question of why hematopoietic cells express these receptors. A tempting hypothetical explanation for this phenomenon is that hematopoietic stem cells are related to subpopulation of migrating primordial germ cells. [Leukemia] Abstract | Full Article Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplants in Acute Myeloid Leukemia Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age. Relapse post allogeneic hematopoietic stem cell transplantation remains an important issue, especially for patients who undergo transplant with residual or refractory disease. In these patients, pre- and post-transplant interventions need to be considered. [Bone Marrow Transplant] Abstract Visit our reviews page to see a complete list of reviews in the hematopoiesis research field. | |
| |
INDUSTRY NEWSSangamo Therapeutics and Pfizer Announce Collaboration for Hemophilia A Gene Therapy Sangamo Therapeutics, Inc. and Pfizer Inc. announced an exclusive, global collaboration and license agreement for the development and commercialization of gene therapy programs for Hemophilia A, including SB-525, one of Sangamo’s four lead product candidates, which Sangamo expects will enter the clinic this quarter. [Sangamo Therapeutics, Inc.] Press Release AbbVie announced results from an analysis of data pooled from three Phase III studies evaluating IMBRUVICA® use in patients with high-risk CLL/SLL: RESONATETM, RESONATETM-2 and HELIOS. In this analysis, CLL/SLL patients with genomic abnormalities that typically put them at high risk for poor outcomes achieved higher complete response rates and overall response rates, as well as longer progression free survival at 24 months and overall survival at 30 months, when treated with IMBRUVICA versus comparator-treated patients. [AbbVie] Press Release The new Phase I pilot study, PLAT-03, will examine the feasibility and safety of administering a second T-cell product intended to increase the long-term persistence of the patient’s chimeric antigen receptor T cells that were reprogrammed to detect and destroy cancer. [Seattle Children’s Hospital] Press Release | |
| |
POLICY NEWSTrump Officials Act to Tilt Federal Science Boards toward Industry Critics say that changes to advisory groups at the Environmental Protection Agency and Department of Interior could restrict or paralyze them. [Nature News] Editorial Biology Needs More Staff Scientists Most research institutions are essentially collections of independent laboratories, each run by principal investigators who head a team of trainees. This scheme has ancient roots and a track record of success. But it is not the only way to do science. Indeed, for much of modern biomedical research, the traditional organization has become limiting. [Nature News] Editorial Revamped ‘Anti-Science’ Education Bills in United States Find Success State and local legislatures in the United States are experimenting with new ways to target the topics taught in science classes, and it seems to be paying dividends. Florida’s legislature approved a bill that would enable residents to challenge what educators teach students. [Nature News] Editorial
| |
EVENTSNEW Hematologic Malignancies Visit our events page to see a complete list of events in the community.
| |
JOB OPPORTUNITIESNEW Associate Director – Translational Development (Celgene Corporation) Full Member Faculty – Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center) Faculty Position – Normal and Malignant Hematopoiesis (Cincinnati Children’s Hospital) Postdoctoral Position – Experimental Leukemia Research (University Children’s Hospital Basel) Postdoctoral Position – Acute Myeloid Leukemia (German Cancer Research Center) Postdoctoral Position – Leukemia Research (VIB-KU Leuven Center for Cancer Biology) Scientist – Biological Function of Hematopoietic Stem Cells/Progenitors (HemoGenyx LLC) Lab Director – Pharmacokinetics (Seattle Cancer Care Alliance) Postdoctoral Fellow – Changes in Hematopoietic Stem Cell Biology (Lund University) Principal Scientist – Immuno Oncology (Celgene Corporation) Associate Director – Translational Development (Celgene Corporation) 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.
| |
Have we missed an important article or publication in Hematopoiesis News? Click here to submit! Comments or suggestions? Submit your feedback here. | |
|
Home Hematopoiesis News Volume 8.19 | May 16 2017