Hematopoiesis News Volume 11.01 | Jan 14 2020

TOP STORY

Vitamin B6 Addiction in Acute Myeloid Leukemia

Researchers performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity was required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Long-Term Ex Vivo Expansion of Mouse Hematopoietic Stem Cells

Scientists described a simple platform for the expansion of functional mouse HSCs ex vivo for >one month under fully defined albumin-free conditions. The culture system affords 236- to 899-fold expansion over the course of a month and was also amenable to clonal analysis of HSC heterogeneity. [Nat Protoc] Full Article

GM-CSF Drives Dysregulated Hematopoietic Stem Cell Activity and Pathogenic Extramedullary Myelopoiesis in Experimental Spondyloarthritis

Investigators showed the HSC gene expression program was biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis. GM-CSF-receptor was increased on HSCs and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. [Nat Commun] Full Article

Bone Marrow Niche-Derived Extracellular Matrix-Degrading Enzymes Influence the Progression of B-Cell Acute Lymphoblastic Leukemia

Hypothesizing that leukemias may instruct the bone marrow microenvironment (BMM) to degrade the extracellular matrix (ECM), researchers showed that matrix metalloproteinase-9 (MMP9)-deficiency in the BMM prolongs survival of mice with BCR-ABL1-induced B-cell acute lymphoblastic leukemia (B-ALL) compared with controls and reduces leukemia-initiating cells. MMP-9-deficiency in the BMM leads to reduced degradation of proteins of the ECM and reduced invasion of B-ALL. [Leukemia] Full Article

An Optimized Full Length FLT3/CD3 Bispecific Antibody Demonstrates Potent Anti-Leukemia Activity and Reversible Hematological Toxicity

The authors developed an anti-FMS-like tyrosine kinase 3 (FLT3)-CD3 IgG-based bispecific antibody with high affinity for FLT3 and long half-life to target FLT3-expressing acute myeloid leukemia blasts, irrespective of FLT3 mutational status. They demonstrated that 7370 has picomolar potency against acute myeloid leukemia cell lines in vitro and in vivo. [Mol Ther] Abstract

Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal

TScientists determined that low protein synthesis within HSCs was associated with elevated proteome quality in vivo. HSCs contained less misfolded and unfolded proteins than myeloid progenitors. [Cell Rep] Abstract | Full Article

A Biomaterial-Based Vaccine Eliciting Durable Tumor-Specific Responses Against Acute Myeloid Leukemia

In mouse models of acute myeloid leukemia (AML), investigators showed that a macroporous-biomaterial vaccine that delivered the cytokine granulocyte-macrophage colony-stimulating factor, the Toll-like-receptor-9 agonist cytosine-guanosine oligodeoxynucleotide and one or multiple leukaemia antigens induced local immune-cell infiltration and activated dendritic cells, evoking a potent anti-AML response. [Nat Biomed Eng] Abstract

Neuroimmune/Hematopoietic Axis with Distinct Regulation by the High-Mobility Group Box 1 in Association with Tachykinin Peptides

Substance P (SP) and neurokinin A (NK-A) were derived from the Tac1 gene that was alternately spliced into four variants. The hematopoietic effects of SP and NK-A were mostly mediated via BM stroma. Array analyses with 2400 genes indicated distinct changes in SP-stimulated bone marrow stroma. [J Immunol Res] Abstract

CLINICAL RESEARCH

Impact of ABO Incompatibility on Outcomes after Haploidentical Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia

A total of 199 severe aplastic anemia patients receiving haploidentical hematopoietic stem cell transplantation from ABO-matched, minor ABO-incompatible, or major ABO-incompatible donors were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. [Bone Marrow Transplant] Abstract

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FLT3 Inhibitors in Acute Myeloid Leukemia: Ten Frequently Asked Questions

Patients with FMS-like tyrosine kinase 3 (FLT3)-ITD have a high risk of relapse and low cure rates. Several FLT3 tyrosine kinase inhibitors have been developed in the last few years with variable kinase inhibitory properties, pharmacokinetics, and toxicity profiles. [Leukemia] Abstract

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Adaptive and Genentech Partner to Use clonoSEQ^® Assay to Measure Minimal Residual Disease as a Primary Endpoint in Phase III Study of Chronic Lymphocytic Leukemia Patients

Adaptive Biotechnologies Corporation announced a multi-year, global diagnostic agreement with Genentech, a member of the Roche Group to utilize Adaptive’s next-generation sequencing-based clonoSEQ^® Assay to assess minimal residual disease status in response to venetoclax in the registrational Phase III CRISTALLO study for the treatment of newly diagnosed people with chronic lymphocytic leukemia (CLL) plus additional future venetoclax studies in CLL. [Adaptive Biotechnologies Corporation] Press Release

Tacitus Therapeutics Launches in Collaboration with Mount Sinai to Develop Stem Cell Therapies for Life-Threatening Diseases

Tacitus Therapeutics has launched in collaboration with the Mount Sinai Health System to develop stem cell therapies initially targeting blood cancers and related clotting disorders. Their first therapy, HSC100, currently is being investigated in a Phase I clinical trial. [Tacitus Therapeutics] Press Release

Positive Final 2-Year Topline Data in Completed DC Vaccine Phase I/II Trial in AML Patients

Medigene AG published topline results from its completed open-label Phase I/II clinical trial of Medigene’s autologous dendritic cell (DC) vaccine in 20 patients with acute myeloid leukemia. [Medigene AG] Press Release

St. Jude Hematologist Akshay Sharma Receives ASH 2020 Scholar Award

Akshay Sharma, MBBS, of St. Jude Children’s Research Hospital, is the recipient of a 2020 Scholar Award from the American Society of Hematology (ASH). One of ASH’s most prestigious research award programs, the ASH Scholar Award provides financial support to an early career hematology researcher. [St. Jude Children’s Research Hospital,] Press Release

FDA and NIH Let Clinical Trial Sponsors Keep Results Secret, Investigation Shows

For 20 years, the US government has urged companies, universities, and other institutions that conduct clinical trials to record their results in a federal database, so doctors and patients can see whether new treatments are safe and effective. [STAT News] Editorial

Protect India’s Universities

For several weeks the world has watched as India’s citizens – including academics and students – have taken to the streets. Tens of thousands have been gathering to read out the preamble to the Indian constitution, as a mark of protest against a discriminatory new citizenship law. [Nature News] Editorial

NEW Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR
February 19-23, 2020
Orlando, Florida, United States

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

NEW Team Leader- Clonal Evolution in Leukemia (Institute of Cancer Research)

Scientist – Hematopoietic Stem and Progenitor Cell Biology (STEMCELL Technologies Inc.)

Team Leader – Clonal Evolution in Leukemia (Institute of Cancer Research)

Faculty Position – Cancer Epidemiology (MD Anderson Cancer Center)

Research Fellow – Hematology & Blood Disorders (New York Blood Center)

Postdoctoral Fellowships – Cancer Research (Harvard Medical School)

Postdoctoral Fellowship – Leukemia (Uniformed Services University of the Health Sciences)

Postdoctoral Fellow – Erythropoiesis (Mount Sinai School of Medicine)

Assistant/Associate Professor – Hematology & Oncology (UC Davis School of Medicine)

Associate/Professor – Hematology & Oncology (UC Davis School of Medicine)

Postdoctoral Fellowship – Leukemia Pathogenesis (BC Cancer)

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