Hematopoiesis News Volume 13.34 | Aug 30 2022

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    Danielle Corrigan
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    2022-08-30 | HN 13.34


    Hematopoiesis News by STEMCELL Technologies
    Vol. 13.34 – 30 August, 2022
    TOP STORY

    Tumor Immune Contexture Is a Determinant of Anti-CD19 CAR T Cell Efficacy in Large B Cell Lymphoma

    Researchers assessed whether tumor immune contexture influenced clinical outcomes after axicabtagene ciloleucel. They evaluated the tumor microenvironment of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 Phase II trial.
    [Nature Medicine]

    Full Article


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    HbS Promotes TLR4-Mediated Monocyte Activation and Pro-Inflammatory Cytokine Production in Sickle Cell Disease

    Using purified human hemoglobin (Hb), the authors demonstrated that cell-free HbS, unlike HbA or heme, was responsible for a major enhancement in the expression of pro-inflammatory cytokines by human monocytes.
    [Blood]

    Abstract

    Preclinical Evaluation of Proteolytic Targeting of LCK as a Therapeutic Approach in T Cell Acute Lymphoblastic Leukemia

    Scientists developed a series of lymphocyte-specific protein tyrosine kinase (LCK) degraders using dasatinib as an LCK ligand and phenyl-glutarimide as a cereblon-directing moiety. Their lead compound SJ11646 exhibited marked efficiency in cereblon-mediated LCK degradation in T cell acute lymphoblastic leukemia cells.
    [Science Translational Medicine]

    Abstract

    A Senescence Stress Secretome Is a Hallmark of Therapy-Related Myeloid Neoplasm Stromal Tissue Occurring Soon after Cytotoxic Exposure

    Researchers performed multi-omic characterization of bone marrow stromal cells from therapy-related myeloid neoplasm patients.
    [Leukemia]

    Full Article

    Concurrent Zrsr2 Mutation and Tet2 Loss Promote Myelodysplastic Neoplasm in Mice

    Using CRISPR/Cas9 genetically engineered mice, investigators demonstrated that Zrsr2m/mTet2−/− promoted myelodysplastic neoplasm with reduced penetrance.
    [Leukemia]

    Full Article

    BCL6 Inhibition Ameliorates Ruxolitinib Resistance in CRLF2-Rearranged Acute Lymphoblastic Leukemia

    To better understand the mechanisms underlying the insufficient efficacy of JAK inhibition, the authors explored gene expression changes upon treatment with a JAK1/2 inhibitor and revealed BCL6 elevation as one such mechanism.
    [Haematologica]

    Abstract

    Targeting Histone Methylation to Reprogram the Transcriptional State That Drives Survival of Drug-Tolerant Myeloid Leukemia Persisters

    Scientists demonstrated that the anthracycline doxorubicin epigenetically reprogrammed leukemia cells by inducing histone 3 lysine 27 (H3K27) and H3K4 tri-methylation.
    [iScience]

    AbstractFull ArticleGraphical Abstract

    Exploring the Mechanistic Link between SF3B1 Mutation and Ring Sideroblast Formation in Myelodysplastic Syndrome

    Splicing factor 3b subunit 1 (SF3B1K700E) expressing cells showed higher proportion of ring sideroblasts (RS) than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation.
    [Scientific Reports]

    Full Article

    Multi-Omics Analysis Defines Highly Refractory RAS Burdened Immature Subgroup of Infant Acute Lymphoblastic Leukemia

    Researchers performed RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia.
    [Nature Communications]

    Full Article

    Survival and Late Effects of Hematopoietic Cell Transplantation in Patients with Thalassemia Major

    Scientists evaluated long-term survival and late effects in 137 patients affected by thalassemia major who received an allogeneic hematopoietic cell transplantation.
    [Bone Marrow Transplantation]

    Full Article

    Sequencing T Cell Redirection Therapies Leads to Deep and Durable Responses in Relapsed/Refractory Myeloma Patients

    Investigators showed that the sequential use of different T cell redirection therapies was possible and could lead to deep and durable responses following relapse after bispecific antibody therapy in relapsed/refractory multiple myeloma.
    [Blood Advances]

    Abstract

    Impact of Lung Function Impairment after Allogeneic Hematopoietic Stem Cell Transplantation

    The authors investigated pulmonary function following hematopoietic stem cell transplantation in terms of its change and the clinical significance of its decline.
    [Scientific Reports]

    Full Article

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    REVIEWS

    Osteoblast Lineage Support of Hematopoiesis in Health and Disease

    Scientists review populations of osteoblasts at differing stages of differentiation and summarize the current understanding of the role of the osteoblast lineage in supporting hematopoiesis.
    [Journal of Bone and Mineral Research]

    Abstract

    The Effect of Hematopoietic Stem Cell Transplantation on Fertility and Strategies for Improvement

    The authors review the impact of HSC transplantation on ovarian function, post-transplant fertility, and birth outcomes, and the contemporaneous strategies to preserve fertility for these patients.
    [Bone Marrow Transplantation]

    Abstract

    INDUSTRY AND POLICY NEWS

    FibroGen Announces Completion of Patient Enrollment in MATTERHORN, a Phase III Clinical Study of Roxadustat for the Treatment of Anemia in Patients with Lower Risk Transfusion-Dependent Myelodysplastic Syndromes (MDS)

    FibroGen, Inc. announced completion of patient enrollment for MATTERHORN, a Phase III clinical study of roxadustat for treatment of anemia in patients with lower risk transfusion-dependent MDS.
    [FibroGen, Inc.]

    Press Release

    Century Therapeutics Receives Study May Proceed Notification from FDA for CNTY-101, the First Allogeneic Cell Therapy Product Candidate Engineered to Overcome Three Major Pathways of Host vs Graft Rejection

    Century Therapeutics, Inc. announced that the company has been notified by the US FDA that the company’s ELiPSE-1 clinical study may proceed to assess CNTY-101 in patients with relapsed or refractory CD19 positive B cell malignancies.
    [Century Therapeutics, Inc.]

    Press Release

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    Olivia Newton-John Cancer Research Institute – Victoria, Australia

    Senior Bioinformatics Research Scientist – Hematopoiesis and Blood Disorders

    St. Jude Children’s Research Hospital – Memphis, Tennessee, United States

    Postdoctoral Scholar – Cancer TCR Gene Therapy

    The University of Chicago – Chicago, Illinois, United States

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