Volume 6.49 | Dec 15

Hematopoiesis News 6.49 December 15, 2015
Hematopoiesis News
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Clearance of Senescent Cells by ABT263 Rejuvenates Aged Hematopoietic Stem Cells in Mice
The authors screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted senescent cells, including senescent bone marrow hematopoietic stem cells and senescent muscle stem cells. [Nat Med] Abstract | Press Release
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PUBLICATIONS (Ranked by impact factor of the journal)
Targeting Casein Kinase II Restores Ikaros Tumor Suppressor Activity and Demonstrates Therapeutic Efficacy in High-Risk Leukemia
Investigators showed that Ikaros function is impaired by the pro-oncogenic casein kinase II (CK2), and that CK2 is overexpressed in leukemia. CK2 inhibition restores Ikaros function as transcriptional repressor of cell cycle and phosphatidylinositol-3 kinase pathway genes, resulting in an antileukemia effect. [Blood]
| Press Release

Brca1 Deficiency Causes Bone Marrow Failure and Spontaneous Hematologic Malignancies in Mice
The authors showed that loss of Brca1 in murine bone marrow causes hematopoietic defects similar to that seen in people with Fanconi anemia. [Blood] Abstract

CBP/Catenin Antagonist Safely Eliminates Drug-Resistant Leukemia-Initiating Cells
Researchers demonstrated that specifically inhibiting the interaction between CREB-binding protein (CBP) and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells, thereby sensitizing them to BCR-ABL tyrosine kinase inhibitors. [Oncogene] Abstract

Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs
Using a combination of DNA mutation indicator assays, researchers observed a 2- to 3-fold increase in the number of DNA mutations in the hematopoietic system upon aging. [Cell Rep] Full Article | Graphical Abstract

Fancb Deficiency Impairs Hematopoietic Stem Cell Function
Scientists investigated hematopoiesis in adult Fancb deficient (Fancb-/y) mice and found that Fancb-/y mice have decreased hematopoietic stem cell quiescence accompanied by reduced progenitor activity in vitro and reduced repopulating capacity in vivo. [Sci Rep] Full Article

Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells
Investigators examined the mechanism underlying the development of KMT2A (MLL)-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. [PLoS One] Full Article


Ibrutinib Combined with Bendamustine and Rituximab Compared with Placebo, Bendamustine, and Rituximab for Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (HELIOS): A Randomized, Double-Blind, Phase III Study
The authors assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton’s tyrosine kinase, to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. [Lancet Oncol] Abstract

Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults with Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study
Scientists evaluated the efficacy of pediatric-like acute lymphoblastic leukemia therapy in adults with lymphoblastic lymphoma. [J Clin Oncol] Abstract

Inotuzumab Ozogamicin in the Management of Acute Lymphoblastic Leukemia
Researchers analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allogeneic stem cell transplantation in a single center. [Bone Marrow Transplant] Abstract

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Molecular Landscapes of Human Hematopoietic Stem Cells in Health and Leukemia
Scientists outline the current understanding of the molecular programs that govern human hematopoietic stem cells (HSCs) and how dynamic changes occurring during HSC differentiation are necessary for well-regulated blood formation under homeostasis and upon injury. [Ann N Y Acad Sci] Abstract

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BioLineRx Announces Regulatory Submission for Phase II Trial of BL-8040 as Novel Stem Cell Mobilization Treatment
BioLineRx Ltd. announced the filing of regulatory submissions required to commence a Phase II trial for BL-8040 as a novel approach for mobilization and collection of bone marrow stem cells from the peripheral blood circulation. [BioLineRx Ltd.] Press Release

Cepheid Announces International Commercial Availability of Next Generation BCR-ABL Test
Cepheid announced the commercial availability outside the United States of Xpert® BCR-ABL Ultra, a quantitative measure of BCR-ABL1 mRNA transcripts that allows physicians to monitor the effectiveness of therapy in their patients with chronic myelogenous leukemia with enhanced sensitivity. [Cepheid] Press Release

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NEW The Controlling Cancer Summit 2016
May 17-19, 2016
London, United Kingdom

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NEW Early Stage Researcher – Immunotherapy (ISPIC Consortium Members)

Full Member Faculty – Hematopoietic Cell Transplant Program (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Leukemia and Lymphoma (Emory University)

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)

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

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