The Epigenetic Regulator RINF (CXXC5) Maintains SMAD7 Expression in Human Immature Erythroid Cells and Sustains Red Blood Cells Expansion

Scientists evaluated the consequences of retinoid-inducible nuclear factor (RINF) silencing on cytokineinduced erythroid differentiation of human primary CD34+ progenitors.
[Haematologica]
Astori, A., Matherat, G., Munoz, I., Gautier, E.-F., Surdez, D., Zermati, Y., Verdier, F., Zaidi, S., Feuillet, V., Kadi, A., Lauret, E., Delattre, O., Lefèvre, C., Fontenay, M., Ségal-Bendirdjian, E., Dusanter-Fourt, I., Bouscary, D., Hermine, O., Mayeux, P., & Pendino, F. (2020). The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion. Haematologica, 0–0. https://doi.org/10.3324/haematol.2020.263558 Cite
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Melanoma Cells Can Be Eliminated by Sialylated CD43 × CD3 Bispecific T Cell Engager Formats In Vitro and In Vivo

To increase the efficacy of AT1413 as a therapeutic antibody, researchers generated two different formats of bispecific T-cell engaging antibodies to both CD43s and CD3ε.
[Cancer Immunology Immunotherapy]
Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo | SpringerLink. (n.d.). Retrieved November 24, 2020, from https://link.springer.com/article/10.1007/s00262-020-02780-9 Cite
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Pivotal Role of DPYSL2A in KLF4-Mediated Monocytic Differentiation of Acute Myeloid Leukemia Cells

The authors report that dihydropyrimidinase like 2 (DPYSL2), also known as CRMP2, was a novel key differentiation mediator downstream of KLF4 in acute myeloid leukemia cells.
[Scientific Reports]
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PharmaTher Expands Patent Portfolio with Filing of US Patent for Novel Use of Psilocybin to Treat Cancer

PharmaTher, Inc. has filed a provisional patent application with the US Patent and Trademark Office outlining the potential novel use of psilocybin to treat cancer, which was discovered by panaceAI™, their proprietary psychedelic drug repurposing artificial intelligence platform.
[PharmaTher, Inc. (GlobeNewswire, Inc.)]
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Venetoclax and Pegcrisantaspase for Complex Karyotype Acute Myeloid Leukemia

Researchers report synergistic anti-leukemic activity of the BCL-2 inhibitor venetoclax and the asparaginase formulation Pegylated Crisantaspase in CK-AML in vitro and in vivo.
[Leukemia]
Emadi, A., Kapadia, B., Bollino, D., Bhandary, B., Baer, M. R., Niyongere, S., Strovel, E. T., Kaizer, H., Chang, E., Choi, E. Y., Ma, X., Tighe, K. M., Carter-Cooper, B., Moses, B. S., Civin, C. I., Mahurkar, A., Shetty, A. C., Gartenhaus, R. B., Kamangar, F., & Lapidus, R. G. (2020). Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. Leukemia, 1–18. https://doi.org/10.1038/s41375-020-01080-6 Cite
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Induction of Differentiation of the Acute Myeloid Leukemia Cell Line (HL-60) by a Securinine Dimer

Scientists found that SN3-L6 induced transdifferentiation of both acute myeloid leukemia and chronic myelogenous leukemia cells but unexpectedly, a new transdifferentiation pathway from acute promyelocytic leukemia cells to morphologically and immunologically normal megakaryocytes and platelets were discovered.
[Cell Death Discovery]
Hou, W., Wang, Z.-Y., Lin, J., & Chen, W.-M. (2020). Induction of differentiation of the acute myeloid leukemia cell line (HL-60) by a securinine dimer. Cell Death Discovery, 6(1), 1–11. https://doi.org/10.1038/s41420-020-00354-3 Cite
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PVRIG Is a Novel NK Cell Immune Checkpoint Receptor in Acute Myeloid Leukemia

Scientists showed that acute myeloid leukemia (AML) patient blasts consistently expressed the poliovirus receptor-related immunoglobulin domain-containing (PVRIG) ligand. Furthermore, PVRIG blockade significantly enhanced NK cell killing of PVRL2+, poliovirus receptorlo AML cell lines, and significantly increased NK cell activation and degranulation in the context of patient primary AML blasts.
[Haematologica]
Li, J., Whelan, S., Kotturi, M. F., Meyran, D., D’Souza, C., Hansen, K., Liang, S., Hunter, J., Trapani, J. A., & Neeson, P. J. (2020). PVRIG is a novel NK cell immune checkpoint receptor in acute myeloid leukemia. Haematologica, 0–0. https://doi.org/10.3324/haematol.2020.258574 Cite
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SYK Inhibition Targets Acute Myeloid Leukemia Stem Cells by Blocking their Oxidative Metabolism

Investigators addressed the consequences of spleen tyrosine kinase (SYK) inhibition to leukemia stem-cell function and assessed SYK-associated pathways in acute myeloid leukemia cell biology.
[Cell Death & Disease]
Polak, A., Bialopiotrowicz, E., Krzymieniewska, B., Wozniak, J., Stojak, M., Cybulska, M., Kaniuga, E., Mikula, M., Jablonska, E., Gorniak, P., Noyszewska-Kania, M., Szydlowski, M., Piechna, K., Piwocka, K., Bugajski, L., Lech-Maranda, E., Barankiewicz, J., Kolkowska-Lesniak, A., Patkowska, E., … Juszczynski, P. (2020). SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism. Cell Death & Disease, 11(11), 1–15. https://doi.org/10.1038/s41419-020-03156-8 Cite
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Hyperglycemia Cooperates with Tet2 Heterozygosity to Induce Leukemia Driven by Pro-Inflammatory Cytokine Induced LncRNA Morrbid

Utilizing a novel mouse model bearing haploinsufficiency of Tet2, to mimic the human pre-leukemic stem and progenitor cells condition and hyperglycemic stress (HG), in the form of an Ins2Akita/+ mutation, which induces HG and type-1 diabetes mellitus, researchers showed that the compound mutant mice develop a lethal form of myeloproliferative neoplasm and/or acute myeloid leukemia.
[Journal of Clinical Investigation]
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DPP4+ Exosomes in AML Patients’ Plasma Suppress Proliferation of Hematopoietic Progenitor Cells

Exosomes isolated from acute myeloid leukemia patients’ plasma at diagnosis significantly and dose-dependently suppressed colony formation of normal hematopoietic progenitor cells.
[Leukemia]
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The IL1-IL1RAP Axis Plays an Important Role in the Inflammatory Leukemic Niche that Favors Acute Myeloid Leukemia Proliferation Over Normal Hematopoiesis.

The IL1β-induced inflammatory secretome of IL1RAPexpressing acute myeloid leukemia (AML) cells grown on a stromal layer of MSCs affected normal hematopoiesis including hematopoietic stem/progenitor cells while AML cell proliferation was not affected.
[Haematologica]
Boer, B. de, Sheveleva, S., Apelt, K., Vellenga, E., Mulder, A. B., Schuringa, G. H., & Jacob, J. (2020). The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis. Haematologica, 0–0. https://doi.org/10.3324/haematol.2020.254987 Cite
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