Using a MLL-AF9 knock-in mouse model, researchers discovered that consumption of a high-fat diet accelerates the risk of developing acute myeloid leukemia.
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Hermetet, F., Mshaik, R., Simonet, J., Callier, P., Delva, L., & Quéré, R. (2020). High-fat diet intensifies MLL-AF9 -induced acute myeloid leukemia through activation of the FLT3 signaling in mouse primitive hematopoietic cells. Scientific Reports, 10(1), 16187. https://doi.org/10.1038/s41598-020-73020-4 Cite
The authors expanded RASGRP1 expression surveys in pediatric T-ALL and generated a RoLoRiG mouse model crossed to Mx1CRE to determine the consequences of induced RASGRP1 overexpression in primary hematopoietic cells.
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Investigators introduced a low-input tagmentation-based Hi-C (tagHi-C) method to capture the chromatin structures of hundreds of cells. Using tagHi-C, they were able to map the spatiotemporal dynamics of chromatin structure in ten primary hematopoietic stem, progenitor, and differentiated cell populations from mouse bone marrow.
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The authors describe the circuitry of a transactivation system responsible for oncogenic self-renewal. MLL recruited RNA polymerase II to unmethylated CpG-rich promoters by its CXXC domain and activated transcription by transcriptional regulators, including the AF4 family/ENL family/P-TEFb complex, DOT1L, and p300/CBP histone acetyl transferases.
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To identify determinants of bone marrow failure, researchers performed single-cell transcriptome profiling of primary hematopoietic stem and progenitor cells from Fanconi anemia patients.
[Cell Stem Cell]
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Rodríguez, A., Zhang, K., Färkkilä, A., Filiatrault, J., Yang, C., Velázquez, M., Furutani, E., Goldman, D. C., Teresa, B. G. de, Garza-Mayén, G., McQueen, K., Sambel, L. A., Molina, B., Torres, L., González, M., Vadillo, E., Pelayo, R., Fleming, W. H., Grompe, M., … D’Andrea, A. D. (2020). MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.09.004 Cite
Apollomics, Inc., announced APL-106 has received Investigational New Drug approval from the China National Medical Products Administration Center for Drug Evaluation. This approval enables the initiation of a Phase I pharmacokinetic and tolerability study and includes acceptance of a Phase III bridging study of APL-106 in combination with chemotherapy in relapsed/refractory acute myeloid leukemia.
Prelude Therapeutics Incorporated announced that the first patient has been dosed in its first-in-human Phase I open-label, multicenter, dose-escalation study of PRT1419 in patients with relapsed/refractory hematologic malignancies. PRT1419, the company’s third clinical candidate, is designed to be an orally available, potent and selective MCL1 inhibitor.
[ Prelude Therapeutics Incorporated ]
Outpatient second hematoprogenitors transplant after reduced‐intensity conditioning at a single academic center was analyzed. Twenty‐seven consecutive adults who received an allogeneic hematopoietic stem cell transplantation (allo‐HSCT) after an initial auto‐ or allo‐HSCT from 2006 to 2019 were included.
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Orchard Therapeutics announced that the European Medicines Agency has granted Priority Medicines designation to OTL-203, an investigational ex vivo autologous hematopoietic stem cell gene therapy in development for the treatment of mucopolysaccharidosis type I at the San Raffaele Telethon Institute for Gene Therapy.
[Orchard Therapeutics plc.]
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Vor Biopharma and Arbor Biotechnologies announced an agreement to use Arbor’s gene editing technologies to engineer hematopoietic stem cells, towards the goal of developing therapies for the treatment of blood cancers, such as acute myeloid leukemia.
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In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells. Whole transcriptome analysis using RNAseq indicated Ambrisentan’s inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile.
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Kappes, L., Amer, R. L., Sommerlatte, S., Bashir, G., Plattfaut, C., Gieseler, F., Gemoll, T., Busch, H., Altahrawi, A., Al-Sbiei, A., Haneefa, S. M., Arafat, K., Schimke, L. F., Khawanky, N. E., Schulze-Forster, K., Heidecke, H., Kerstein-Staehle, A., Marschner, G., Pitann, S., … Cabral-Marques, O. (2020). Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis. Scientific Reports, 10(1), 15931. https://doi.org/10.1038/s41598-020-72960-1 Cite