Hematopoiesis News Volume 12.33 | Aug 24 2021

May 12, 2022

2021-08-24 | HN 12.33

Hematopoiesis News by STEMCELL Technologies

Vol. 12.33 – 24 August, 2021

TOP STORY

A Phase III, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML after ≥ Two Prior TKIs

In this Phase III, open-label study, patients with chronic myeloid leukemia (CML) in chronic phase previously treated with ≥ two tyrosine kinase inhibitors (TKIs) were randomized to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily.
[Blood]

Abstract

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PUBLICATIONSRanked by the impact factor of the journal

A Unified Model of Human Hemoglobin Switching through Single-Cell Genome Editing

Researchers described a single-cell genome editing functional assay that enabled specific mutations to be recapitulated individually and in combination, providing insights into how multiple mutation-harboring functional elements collectively contributed to fetal hemoglobin expression.
[Nature Communications]

Full Article

Effective Control of Large Deletions after Double-Strand Breaks by Homology-Directed Repair and dsODN Insertion

The authors showed that large deletions were ubiquitous but were dependent on editing sites and cell types. Human primary T cells displayed more significant deletions than hematopoietic stem and progenitor cells, whereas they observed low levels in induced pluripotent stem cells.
[Genome Biology]

Full Article

TET2 as a Tumor Suppressor and Therapeutic Target in T-Cell Acute Lymphoblastic Leukemia

Investigators analyzed RNA-sequencing data of 321 primary T-cell acute lymphoblastic leukemias (T-ALLs), 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 was transcriptionally repressed or silenced in 71% and 17% of T-ALL, respectively.
[Proceedings of the National Academy of Sciences of the United States of America]

Full Article

Membrane-Bound SCF and VCAM-1 Synergistically Regulate the Morphology of Hematopoietic Stem Cells

Scientists used a supported lipid bilayer (SLB) to recapitulate the membrane-bound interactions between HSCs and niche stromal cells. HSCs clustered membrane-bound stem cell factor (SCF) at the HSC-SLB interface.
[Journal of Cell Biology]

Full Article

The Fibronectin-ILT3 Interaction Functions as a Stromal Checkpoint That Suppresses Myeloid Cells

Using a screening approach, the authors identified fibronectin as a functional ligand for immunoglobulin-like transcript 3 (ILT3). The interaction of fibronectin with ILT3 polarized myeloid cells toward a suppressive state, and these effects were reversed with an ILT3-specific antibody that blocked the interaction of ILT3 with fibronectin.
[Cancer Immunology Research]

Abstract

A Histone Modifier, ASXL1, Interacts with NONO and Is Involved in Paraspeckle Formation in Hematopoietic Cells

Paraspeckles were disrupted and Nono localization was abnormal in the cytoplasm of hematopoietic stem and progenitor cells (HSPCs) derived from ASXL1-MT knockin mice. Nono depletion and the forced expression of cytoplasmic NONO impaired the repopulating potential of HSPCs, as did ASXL1-MT.
[Cell Reports]

Full Article Graphical Abstract

Fetal Hematopoietic Stem Cell Homing Is Controlled by VEGF Regulating the Integrity and Oxidative Status of the Stromal-Vascular Bone Marrow Niches

By studying physiological homing of fetal hematopoietic stem and progenitor cells (HSPCs), scientists showed the critical requirement of balanced local crosstalk within the skeletal niche for successful HSPC settlement in bone marrow.
[Cell Reports]

Full Article Graphical Abstract

LncRNA KCNQ1OT1 Activated by C-Myc Promotes Cell Proliferation via Interacting with FUS to Stabilize MAP3K1 in Acute Promyelocytic Leukemia

Functional assays demonstrated that knockdown of KCNQ1OT1 reduced acute promyelocytic leukemia cell proliferation and increased apoptosis. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA.
[Cell Death & Disease]

Full Article

Thrombopoietin-Based CAR-T Cells Demonstrate In Vitro and In Vivo Cytotoxicity to MPL Positive Acute Myelogenous Leukemia and Hematopoietic Stem Cells

CAR T cells were designed using a ligand binding domain instead of a single chain variable fragments to target stem-like leukemia cells. Thrombopoietin, the natural ligand to the myeloproliferative leukemia protein (MPL) receptor, was used as the antigen binding domain to engage MPL expressed on HSCs and erythropoietic and megakaryocytic acute myeloid leukemias.
[Gene Therapy]

Full Article

CLINICAL RESEARCH

Up-Regulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Cancer Patients

Researchers conducted a Phase I trial in 36 patients with hepatocellular carcinoma who were given therapeutic C/EBPα saRNA (MTL-CEBPA) as either neoadjuvant or adjuvant treatment. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell numbers.
[Clinical Cancer Research]

Abstract

Final Results of a Phase II Clinical Trial of LCL161, an Oral SMAC Mimetic for Patients with Myelofibrosis

Investigators conducted a single-center, investigator-initiated Phase II clinical trial, with a monovalent SMAC mimetic LCL161 in patients with intermediate to high-risk myelofibrosis.
[Blood Advances]

Full Article
Graphical Abstract

Benign and Malignant Hematologic Manifestations in Patients with VEXAS Syndrome Due to Somatic Mutations in UBA1

Patients with VEXAS syndrome had a propensity toward developing cytopenia, myelodysplastic syndrome, multiple myeloma, and venous thromboembolism. Bone marrow from patients with VEXAS showed characteristic vacuolization of myeloid and erythroid precursors.
[Blood Advances]

Full Article Graphical Abstract

The StemSpan™ T Cell Generation Kit is designed to promote differentiation of HSPCs into T cells in stroma- and serum-free culture conditions.

REVIEWS

Interactions of Adenoviruses with Platelets and Coagulation and the Vaccine-Associated Autoimmune Thrombocytopenia Thrombosis Syndrome

The authors review the interactions between adenoviral vectors and the hemostatic system of possible relevance for the vaccine associated thrombotic thrombocytopenia syndrome, analyze systematically the clinical data on the reported thrombotic complications of adenovirus-based therapeutics, and discuss all the current hypotheses on the mechanisms triggering this novel syndrome.
[Haematologica]

Abstract

Novel CAR T Therapy Is a Ray of Hope in the Treatment of Seriously Ill AML Patients

Scientists discuss and explain the most recent advances in chimeric antigen receptor (CAR) T cell-based therapies targeting acute myeloid leukemia (AML) antigens and review the results of preclinical and clinical trials.
[Stem Cell Research & Therapy]

Full Article

INDUSTRY AND POLICY NEWS

Biosight Announces Initiation of Investigator Sponsored Phase II Clinical Trial of Aspacytarabine for Relapsed/Refractory AML and MDS with the Groupe Francophone Des Myélodysplasies

Biosight Ltd. announced the initiation of a Phase II trial to evaluate aspacytarabine, Biosight’s proprietary antimetabolite, as a second line treatment for patients with relapsed or refractory myelodysplastic syndrome or acute myeloid leukemia.
[Biosight Ltd. (Globe Newswire)]

Press Release

Galecto Announces First Patient Treated in Phase IIa Trial of the Oral LOXL2 Inhibitor GB2064 in Myelofibrosis (the MYLOX-1 Trial)

Galecto, Inc. announced the treatment of the first patient in a Phase IIa trial of its oral LOXL2 inhibitor GB2064 in myelofibrosis. The current standard of care for myelofibrosis is JAK inhibitors, but questions remain regarding side effects caused by the mechanism of action.
[Galecto, Inc.]

Press Release

US Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Orencia (abatacept) for the Prevention of Acute Graft Versus Host Disease (aGvHD)

Bristol Myers Squibb announced that the FDA has accepted its supplemental Biologics License Application for Orencia for the prevention of moderate to severe aGvHD in patients six years of age and older receiving unrelated donor hematopoietic stem cell transplantation.
[Bristol Myers Squibb]

Press Release

FEATURED EVENT

A Phase III, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML after ≥ Two Prior TKIs

A Unified Model of Human Hemoglobin Switching through Single-Cell Genome Editing

Effective Control of Large Deletions after Double-Strand Breaks by Homology-Directed Repair and dsODN Insertion

TET2 as a Tumor Suppressor and Therapeutic Target in T-Cell Acute Lymphoblastic Leukemia

Membrane-Bound SCF and VCAM-1 Synergistically Regulate the Morphology of Hematopoietic Stem Cells

The Fibronectin-ILT3 Interaction Functions as a Stromal Checkpoint That Suppresses Myeloid Cells

A Histone Modifier, ASXL1, Interacts with NONO and Is Involved in Paraspeckle Formation in Hematopoietic Cells

Fetal Hematopoietic Stem Cell Homing Is Controlled by VEGF Regulating the Integrity and Oxidative Status of the Stromal-Vascular Bone Marrow Niches

LncRNA KCNQ1OT1 Activated by C-Myc Promotes Cell Proliferation via Interacting with FUS to Stabilize MAP3K1 in Acute Promyelocytic Leukemia

Thrombopoietin-Based CAR-T Cells Demonstrate In Vitro and In Vivo Cytotoxicity to MPL Positive Acute Myelogenous Leukemia and Hematopoietic Stem Cells

Up-Regulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Cancer Patients

Final Results of a Phase II Clinical Trial of LCL161, an Oral SMAC Mimetic for Patients with Myelofibrosis

Benign and Malignant Hematologic Manifestations in Patients with VEXAS Syndrome Due to Somatic Mutations in UBA1

Interactions of Adenoviruses with Platelets and Coagulation and the Vaccine-Associated Autoimmune Thrombocytopenia Thrombosis Syndrome

Novel CAR T Therapy Is a Ray of Hope in the Treatment of Seriously Ill AML Patients

Biosight Announces Initiation of Investigator Sponsored Phase II Clinical Trial of Aspacytarabine for Relapsed/Refractory AML and MDS with the Groupe Francophone Des Myélodysplasies

Galecto Announces First Patient Treated in Phase IIa Trial of the Oral LOXL2 Inhibitor GB2064 in Myelofibrosis (the MYLOX-1 Trial)

US Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Orencia (abatacept) for the Prevention of Acute Graft Versus Host Disease (aGvHD)

American Association of Blood Banks (AABB)

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Postdoctoral Fellow – Normal and Leukemic Hematopoietic Stem Cells

Development Engineer – Cell Therapies and Regenerative Medicine

Postdoctoral Associate – Stem/Progenitor Cells

Faculty Position – Cancer Biology and Signal Transduction

Research Associate – Cell and Regenerative Biology

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