The Role of Mitochondrial Proteases in Leukemic Cells and Leukemic Stem Cells

Investigators highlight the functional consequences of inhibiting and activating mitochondrial proteases and discuss their potential as therapeutic targets in acute myeloid leukemia.
[Stem Cells Translational Medicine]
Mirali, S., & Schimmer, A. D. (n.d.). The role of mitochondrial proteases in leukemic cells and leukemic stem cells. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/10.1002/sctm.20-0142 Cite
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Prognostic Impact of TP53 Mutation, Monosomal Karyotype, and Prior Myeloid Disorder in Nonremission Acute Myeloid Leukemia at allo-HSCT

Researchers analyzed prognostic gene mutations by targeted next-generation sequencing to identify predisposing factors for predicting overall survival at one month before transplantation. They enrolled 120 patients with nonremission acute myeloid leukemia who underwent first allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2005 and 2018.
[Bone Marrow Transplantation]
Najima, Y., Sadato, D., Harada, Y., Oboki, K., Hirama, C., Toya, T., Doki, N., Haraguchi, K., Yoshifuji, K., Akiyama, M., Inamoto, K., Igarashi, A., Kobayashi, T., Kakihana, K., Okuyama, Y., Sakamaki, H., Harada, H., & Ohashi, K. (2020). Prognostic impact of TP53 mutation, monosomal karyotype, and prior myeloid disorder in nonremission acute myeloid leukemia at allo-HSCT. Bone Marrow Transplantation, 1–13. https://doi.org/10.1038/s41409-020-01016-9 Cite
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Biosight Granted US FDA Fast Track Designation for BST-236 for the Treatment of Acute Myeloid Leukemia

Biosight Ltd. announced that that the FDA has granted Fast Track designation for BST-236 for the treatment of acute myeloid leukemia in adults who are 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
[Biosight Ltd. (GlobeNewswire, Inc.)]
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Allogeneic Hematopoietic Cell Transplantation Efficacy in Patients with Philadelphia Chromosome-Positive Acute Myeloid Leukemia in Complete Remission

Researchers retrospectively analyzed 4649 acute myeloid leukemia (AML) patients who received allogeneic hematopoietic cell transplantation and were in complete remission. Outcomes of Philadelphia chromosome-positive AML, intermediate-risk, and poor-risk AML patients were compared.
[Bone Marrow Transplantation]
Mizuno, S., Yanada, M., Kawamura, K., Masuko, M., Uchida, N., Ozawa, Y., Iwato, K., Ohashi, K., Ikegame, K., Kim, S.-W., Tanaka, M., Eto, T., Kanda, Y., Fukuda, T., Atsuta, Y., Yano, S., & Takami, A. (2020). Allogeneic hematopoietic cell transplantation efficacy in patients with Philadelphia chromosome-positive acute myeloid leukemia in complete remission. Bone Marrow Transplantation, 1–11. https://doi.org/10.1038/s41409-020-01011-0 Cite
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Cleave Therapeutics Announces Commencement of a Phase I Clinical Study of CB-5339, A Valosin-Containing Protein (VCP)/p97 Inhibitor, in Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Cleave Therapeutics, Inc. announced that the first patient has been dosed with CB-5339 in a Phase I clinical trial of patients with relapsed/refractory AML or relapsed/refractory intermediate or high-risk MDS.
[Cleave Therapeutics, Inc.]
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Ascentage Pharma Announces First Patient Dosed in the Phase Ib Study of MDM2-p53 Inhibitor APG-115 as Single Agent and in Combinations for the Treatment of Hematologic Malignancies in China

Ascentage Pharma announced that the Phase Ib study of the company’s novel MDM2-p53 inhibitor candidate APG-115 as a single agent or in combinations for the treatment of Chinese patients with relapsed/refractory acute myeloid leukemia, or relapsed/progressed high/very high risk myelodysplastic syndrome has dosed its first patient in China.
[Ascentage Pharma]
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Sufficiency for Inducible Caspase-9 Safety Switch in Human Pluripotent Stem Cells and Disease Cells

Researchers used targeted gene editing to introduce the inducible Caspase-9 system into human iPSCs, and then interrogated the efficiency of inducible apoptosis with normal iPSCs as well as diseased iPSCs derived from patients with acute myeloid leukemia.
[Gene Therapy]
Nishimura, T., Xu, H., Iwasaki, M., Karigane, D., Saavedra, B., Takahashi, Y., Suchy, F. P., Monobe, S., Martin, R. M., Ohtaka, M., Nakanishi, M., Burrows, S. R., Cleary, M. L., Majeti, R., Shibuya, A., & Nakauchi, H. (2020). Sufficiency for inducible Caspase-9 safety switch in human pluripotent stem cells and disease cells. Gene Therapy, 1–10. https://doi.org/10.1038/s41434-020-0179-z Cite
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Karolinska Development’s Portfolio Company Aprea Therapeutics Expands Clinical Trial of Eprenetapopt for TP53 Mutant Acute Myeloid Leukemia

Karolinska Development AB announces that its portfolio company Aprea Therapeutics has decided to expand the enrollment of patients in its Phase I clinical trial evaluating eprenetapopt in TP53 mutant acute myeloid leukemia.
[Karolinska Development AB]
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DDX5-Targeting Fully Human Monoclonal Autoantibody Inhibits Proliferation and Promotes Differentiation of Acute Promyelocytic Leukemia Cells by Increasing ROS Production

2F5 was confirmed to induce G0/G1 phase arrest in acute promyelocytic leukemia (APL) cells, and promoted APL cell differentiation combined with decreased DDX5 expression and increased reactive oxygen species production. Knockdown of DDX5 by siRNA also inhibited proliferation, promoted cell differentiation and enhanced ROS production in APL cells.
[Cell Death & Disease]
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HUWE1 Cooperates with RAS Activation to Control Leukemia Cell Proliferation and Human Hematopoietic Stem Cells Differentiation Fate

To understand the role of HUWE1 in human hematopoietic stem and progenitor cells scientists constitutively expressed KRASG12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures.
[Cancer Gene Therapy]
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Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells

The authors showed that a lncRNA, MORRBID, a selective transcriptional repressor of BIM, was overexpressed in human acute myeloid leukemia, which is associated with poor overall survival.
[Cell Reports]
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HSPG2 Overexpression Independently Predicts Poor Survival in Patients with Acute Myeloid Leukemia

The mRNA expression level of heparan sulfate proteoglycan 2 (HSPG2) in bone marrow mononuclear cells and CD34+ hematopoietic stem/progenitor cells obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR.
[Cell Death & Disease]
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