Hematopoiesis News Volume 10.19 | May 21 2019

TOP STORY

EGFR Is Required for Wnt9a-Fzd9b Signaling Specificity in Hematopoietic Stem Cells

Scientists determined that Wnt9a signaled specifically through Fzd9b to elicit β-catenin-dependent Wnt signaling that regulates hematopoietic stem and progenitor cell emergence. They demonstrated that the epidermal growth factor receptor (EGFR) was required as a cofactor for Wnt9a-Fzd9b signaling. [Nat Cell Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

Identification and Transcriptome Analysis of Erythroblastic Island Macrophages

Given that Epo is essential for erythropoiesis and that Epor is expressed in numerous non-erythoid cells, researchers hypothesized that erythroblastic island (EBI) macrophages express Epor so that Epo can act on both erythroid cells and EBI macrophages simultaneously to ensure efficient erythropoiesis. To test this notion, they employed an Epor-eGFPcre knockin mouse model. [Blood] Abstract

Cysteine Depletion Targets Leukemia Stem Cells through Inhibition of Electron Transport Complex II

Loss of succinate dehydrogenase A glutathionylation impaired electron transport chain complex II activity, thereby inhibiting oxidative phosphorylation, reducing production of ATP and leading to leukemia stem cell death. [Blood] Abstract

Secreted Nuclear Protein DEK Regulates Hematopoiesis through CXCR2 Signaling

Investigators demonstrated that extracellular DEK greatly enhanced ex vivo expansion of cytokine-stimulated human and mouse HSCs and regulated HSC and hematopoietic progenitor cell numbers in vivo and in vitro as determined both phenotypically and functionally. [J Clin Invest] Full Article

Targeting VLA4 Integrin and CXCR2 Mobilizes Serially Repopulating Hematopoietic Stem Cells

Researchers sought to improve HSC transplantation by developing a new mobilization strategy in mice through combined targeting of the chemokine receptor CXCR2 and the very late antigen 4 (VLA4) integrin. Rapid and synergistic mobilization of hematopoietic stem and progenitor cells along with an enhanced recruitment of true HSCs was achieved when a CXCR2 agonist was co-administered in conjunction with a VLA4 inhibitor. [J Clin Invest] Abstract | Full Article

A High-Throughput Screen Indicates Gemcitabine and JAK Inhibitors May Be Useful for Treating Pediatric AML

The authors report therapeutics not currently used to treat acute myeloid leukemia (AML), gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors were selective for acute megakaryoblastic leukemia and significantly prolonged survival in multiple preclinical models. [Nat Commun] Full Article

Pro-Inflammatory Cytokine Blockade Attenuates Myeloid Expansion in a Murine Model of Rheumatoid Arthritis

Scientists identified systemic inflammation and myeloid overproduction associated with activation of a myeloid differentiation gene program in HSCs. Surprisingly, despite ongoing inflammation, HSCs from arthritic mice remained in a quiescent state associated with activation of a proliferation arrest gene program. [Haematologica] Full Article

Loss of RAF Kinase Inhibitor Protein Is Involved in Myelomonocytic Differentiation and Aggravates RAS-Driven Myeloid Leukemogenesis

Researchers showed that RAF kinase inhibitor protein (RKIP) loss was functionally involved in myelomonocytic lineage commitment and drove the myelomonocytic differentiation of hematopoietic stem and progenitor cells. These results could be confirmed in vivo, where Rkip deletion induced a myelomonocytic differentiation bias in mice by amplifying the effects of granulocyte-macrophage-colony-stimulating factor. [Haematologica] Full Article

CLINICAL RESEARCH

The First-in-Human Study of the Pan-PIM Kinase Inhibitor PIM447 in Patients with Relapsed and/or Refractory Multiple Myeloma

In the multicenter, open-label, first-in-human study, patients with relapsed and/or refractory multiple myeloma were enrolled to determine the maximum-tolerated dose or recommended dose, safety, pharmacokinetics, and preliminary anti-myeloma activity of PIM447. [Leukemia] Abstract

CD22 CAR T-Cell Therapy in Refractory or Relapsed B Acute Lymphoblastic Leukemia

Investigators conducted a CD22 CAR T-cell therapy in 34 relapsed or refractory B-ALL pediatric and adult patients who failed from previous CD19 CAR T-cell therapy. Complete remission (CR) or CR with incomplete count recovery was achieved in 24 of 30 patients that could be evaluated on day 30 after infusion, which accounted for 70.5% of all 34 enrolled patients. [Leukemia] Abstract

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Integrating Precision Medicine through Evaluation of Cell of Origin in Treatment Planning for Diffuse Large B-Cell Lymphoma

With advanced methodology to determine cell of origin (COO) in a real-world clinical setting, therapies targeted to specific subtypes are under development. The authors review applications of precision medicine exemplified by COO determination in diffuse large B-cell lymphoma patients. [Blood Cancer J] Full Article

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

GBT Announces Upcoming Data Presentations

Global Blood Therapeutics, Inc. (GBT) announced that data supporting the company’s voxelotor program in sickle cell disease will be presented. Three abstracts have been accepted for presentation, including new 24-week efficacy and safety data from approximately 270 patients in the Phase III HOPE Study. [Press release from Global Blood Therapeutics, Inc. discussing research to be presented at the 24^th European Hematology Association (EHA) Congress, Amsterdam] Press Release

Imago BioSciences to Present First Clinical Data for IMG-7289

Imago BioSciences, Inc. announced that an abstract describing clinical data regarding their lysine-specific demethylase inhibitor has been selected for an oral presentation. [Press release from Imago BioSciences, Inc. (Business Wire, Inc.) discussing research to be presented at the 24^th European Hematology Association (EHA) Congress, Amsterdam] Press Release

Bluebird Bio to Present New Data from Clinical Studies of LentiGlobin™ Gene Therapy for Transfusion-Dependent β-Thalassemia (TDT) and LentiGlobin Gene Therapy for Sickle Cell Disease (SCD)

bluebird bio will present data from its clinical studies of LentiGlobin™ gene therapy for TDT including updated results up to 54 months from the long-term follow-up period of the completed Phase I/II Northstar study. [Press release from bluebird bio, Inc. discussing research to be presented at the 24^th European Hematology Association (EHA) Congress, Amsterdam] Press Release

Stemline Therapeutics Announces ELZONRIS Clinical Data Selected for Presentation

Stemline Therapeutics, Inc. announced that ELZONRIS clinical data in blastic plasmacytoid dendritic cell neoplasm, chronic myelomonocytic leukemia, and myelofibrosis have been selected for poster presentations. [Press release from Stemline Therapeutics, Inc. discussing research to be presented at the 24^th European Hematology Association (EHA) Congress, Amsterdam] Press Release

Genmab Announces Data to Be Presented

Genmab A/S announced that 15 industry sponsored abstracts regarding Genmab programs were accepted for presentation. [Press release from Genmab A/S discussing research to be presented at the 24^th European Hematology Association (EHA) Congress, Amsterdam] Press Release

Verastem Oncology to Present New COPIKTRA™ (Duvelisib) Dose Modification Data from Patients Treated in the Phase III DUO Study

Verastem, Inc. announced a poster highlighting dose modification data from the Phase III DUO study evaluating COPIKTRA in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma after at least two prior therapies. [Press release from Verastem, Inc. discussing research to be presented at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting, Chicago] Press Release

Achillion Reports Positive Interim Data for ACH-4471 Phase II Combination Trial with Eculizumab

Achillion Pharmaceuticals, Inc. reported interim data from a Phase II paroxysmal nocturnal hemoglobinuria trial assessing the safety and effectiveness of its oral small molecule factor D inhibitor ACH-4471 in combination with intravenous eculizumab. [Press release from Achillion Pharmaceuticals, Inc. discussing research presented at The New Era of Aplastic Anemia and PNH Meeting, Naples] Press Release

Cellectar Expands Third Cohort of Its Phase II CLOVER-1 Study of CLR 131

Cellectar Biosciences, Inc. announced that initial results from the third cohort of its ongoing Phase II CLOVER-1 study of CLR 131 have exceeded its pre-specified performance criteria. As a result, the company will expand the number of chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphoma patients it will enroll in the cohort. [Cellectar Biosciences, Inc.] Press Release

AbbVie Announces US FDA Approval of VENCLEXTA^® (Venetoclax) as a Chemotherapy-Free Combination Regimen for Previously Untreated Chronic Lymphocytic Leukemia Patients

AbbVie announced that the FDA has approved VENCLEXTA^® in combination with obinutuzumab for previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. The CLL14 trial demonstrated superior progression-free survival as assessed by an independent review committee in patients treated with VENCLEXTA plus obinutuzumab compared to patients who received chlorambucil plus obinutuzumab, a commonly used standard of care. [AbbVie Inc.] Press Release

Celgene Receives European Commission Approvals for REVLIMID^® (Lenalidomide) and IMNOVID^® (Pomalidomide)-Based Triplet Combination Regimens for Patients with Multiple Myeloma

Celgene Corporation announced that the European Commission has approved two new triplet regimens based on Celgene’s proprietary IMiD treatments, REVLIMID and IMNOVID. REVLIMID in combination with bortezomib and dexamethasone, is now indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. [Celgene Corporation] Press Release

Oncopeptides to Apply for Accelerated Approval in the US

Oncopeptides AB announced that, after discussions with the FDA, the company has initiated the preparation for submitting a New Drug Application for accelerated approval of melflufen for the treatment of patients with triple-class refractory multiple myeloma. The company targets to submit the application in the first quarter of 2020. [Oncopeptides AB] Press Release

NSF, NASA, NIST Would Get Funding Boosts under House Spending Bill

The National Science Foundation (NSF) would get a 7% budget increase, and NASA a 3.8% bump, under a 2020 spending bill approved by an appropriations panel of the US House of Representatives. The bill rejects cuts to those and other federal research agencies proposed by President Donald Trump’s administration. [ScienceInsider] Editorial

National Cancer Institute Will Stop Funding Nanotechnology Centers

The end to funding represents a “natural transition” from putting dedicated support into an emerging field to becoming a more mature research field that fits in with other cancer fields, says Piotr Grodzinski of the National Cancer Institute’s Nanodelivery Systems and Devices Branch, which oversees the Centers of Cancer Nanotechnology Excellence, to Science. [The Scientist] Editorial

NEW ESH 5^th International Conference on Acute Myeloid Leukemia – Molecular and Translational: Advances in Biology and Treatment
October 24-26, 2019
Estoril, Portugal

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

NEW Postdoctoral Scientist – Hematopoietic Stem Cell Research (DKFZ / HI-STEM)

NEW Postdoctoral Scientist – Inflammatory Stress in the Bone Marrow (DKFZ / HI-STEM)

Postdoctoral Fellow – Molecular Mechanisms of Myeloma (City of Hope)

Postdoctoral Research Fellow – Translational Gene Therapy & Hematopoietic Stem Cell Research (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Stem Cell Transplantation Cell Interaction (University of Illinois at Chicago)

Assistant Professor – Lymphoma/Myeloma Research (The University of Texas MD Anderson Cancer Center)

Tenure Track Senior Investigator – Malignant Hematology (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellows – Hematological Malignancies & Cancer Immunology (Fox Chase Cancer Center)

Postdoctoral Fellowship – Myeloma Research (University of Calgary)

Postdoctoral Position – Transcriptional Regulation in Leukemia (VIB KU Leuven)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

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