ArticleHaematologica2021
Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Mesenchymal stromal cells modulate survival and regeneration of human hematopoietic stem cells via PGE2/cAMP signaling.Cell death & disease · 2026Article
- Superior Efficacy and Deep Molecular Remission with Venetoclax Plus Hypomethylating Agent in Elderly Acute Myeloid Leukemia: A Real-World Comparative Cohort Study.Clinical pharmacology : advances and applications · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches.Frontiers in pharmacology · 2025Review
- Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.Current pharmacology reports · 2024Article
- BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia.Leukemia · 2024Article
- PLK1 as a cooperating partner for BCL2-mediated antiapoptotic program in leukemia.Blood cancer journal · 2023Article
- PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis.The Journal of clinical investigation · 2023Article
- Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.International journal of molecular sciences · 2023Article
- What can we learn from mice lacking pro-survival BCL-2 proteins to advance BH3 mimetic drugs for cancer therapy?Cell death and differentiation · 2022Review
- Potent, p53-independent induction of NOXA sensitizes MLL-rearranged B-cell acute lymphoblastic leukemia cells to venetoclax.Oncogene · 2022Article
- Extrinsic interactions in the microenvironment in vivo activate an antiapoptotic multidrug-resistant phenotype in CLL.Blood advances · 2021Article
- Pharmacologic Targeting of Mcl-1 Induces Mitochondrial Dysfunction and Apoptosis in B-Cell Lymphoma Cells in aClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Metformin exerts a synergistic effect with venetoclax by downregulating Mcl-1 protein in acute myeloid leukemia.Journal of Cancer · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already FDA-approved, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNAi and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming HSPCs already at inhibitor concentrations of 0.1 μM each, indicating "synthetic lethality" of the two BH3-mimetics in the hematopoietic system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.