A Humanized Animal Model Predicts Clonal Evolution and Therapeutic Vulnerabilities in Myeloproliferative Neoplasms

The authors presented a humanized animal model of myelofibrosis patient-derived xenografts which were robustly engrafted patient cells that recapitulated the patient’s genetic hierarchy and pathologies such as reticulin fibrosis and propagation of myeloproliferative neoplasms-initiating stem cells.
[Cancer Discovery]
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Targeting CD38 in Acute Myeloid Leukemia Interferes with Leukemia Trafficking and Induces Phagocytosis

In line with a predominantly microenvironment-mediated activity of daratumumab in acute myeloid leukemia (AML), CD38 inhibition significantly induced antibody-dependent phagocytosis and showed interference with AML cell trafficking in vivo in a xenograft transplantation model, but overall lacked robust anti-leukemic effects.
[Scientific Reports]
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Acute Myeloid Leukemia Maturation Lineage Influences Residual Disease and Relapse Following Differentiation Therapy

Researchers indicated that relapse can originate from therapy-resistant mature acute myeloid leukemia cells, and suggested differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.
[Nature Communications]
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Biosight Announces Initiation of Phase II Clinical Trial of Aspacytarabine for MDS and AML

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 (MDS) or acute myeloid leukemia (AML).
[Biosight Ltd. (GlobeNewswire, Inc.)]
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CD33-Directed Immunotherapy with Third-Generation Chimeric Antigen Receptor T Cells and Gemtuzumab Ozogamicin in Intact and CD33-Edited Acute Myeloid Leukemia and Hematopoietic Stem and Progenitor Cells

Investigators introduced a CD33-directed third-generation CAR T cell product for the treatment of patients with acute myeloid leukemia.
[International Journal of Cancer]
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Therapeutic Inhibition of GAS6-AS1/YBX1/MYC Axis Suppresses Cell Propagation and Disease Progression of Acute Myeloid Leukemia

Gain or loss of functional leukemia cell models were produced, and in vitro and in vivo experiments were applied to demonstrate its leukemogenic phenotypes.
[Journal of Experimental & Clinical Cancer Research]
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Demethylating Therapy Increases Anti-CD123 CAR T Cell Cytotoxicity against Acute Myeloid Leukemia

Investigators indicated that 5′-Azacitidine increased the immunogenicity of acute myeloid leukemia cells, enhancing recognition and elimination of malignant cells by highly efficient CTLA-4negative anti-CD123 chimeric antigen receptor (CAR) T cells.
[Nature Communications]
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TCP1 Increases Drug Resistance in Acute Myeloid Leukemia by Suppressing Autophagy via Activating AKT/mTOR Signaling

Scientists discovered that the T-complex protein 1 (TCP1) expression was elevated in acute myeloid leukemia patients and high TCP1 expression was associated with low complete response rate along with poor overall survival.
[Cell Death & Disease]
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piggyBac System to Co-Express NKG2D CAR and IL-15 to Augment the In Vivo Persistence and Anti-AML Activity of Human Peripheral Blood NK Cells

Using a non-viral piggyBac transposon technology and human peripheral blood derived primary natural killer (NK) cells, scientists generated CAR-NK cells to target NKG2D ligands.
[Molecular Therapy-Methods & Clinical Development]
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Demethylating Therapy Increases Anti-CD123 CAR T Cell Cytotoxicity against Acute Myeloid Leukemia

The authors developed third-generation anti-CD123 CAR T cells with a humanized CSL362-based ScFv and a CD28-OX40-CD3ζ intracellular signaling domain.
[Nature Communications]
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Asxl1loss Cooperates with Oncogenic Nras in Mice to Reprogram Immune Microenvironment and Drive Leukemic Transformation

Investigators showed that concurrent ASXL1 and NRAS mutations defined a population of chronic myelomonocytic leukemia patients with shorter leukemia-free survival than those with ASXL1 mutation only.
[Blood]
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