ArticleCell death & disease2016
MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
- Mcl1 as a Molecular Switch Linking Inflammatory Bowel Diseases to Colorectal Tumorigenesis.Biomolecules · 2026Review
- Long-lived IgE plasma cells persist in secondary lymphoid tissues using a navitoclax-sensitive survival program.Immunity · 2025Article
- Constructing Cell-Specific Causal Networks of Individual Cells for Depicting Dynamical Biological Processes.Research (Washington, D.C.) · 2025Article
- Single-cell RNA-sequencing analysis of immune and mesenchymal cell crosstalk in the developing enthesis.Scientific reports · 2024Article
- Genes with differential expression across ancestries are enriched in ancestry-specific disease effects likely due to gene-by-environment interactions.American journal of human genetics · 2024Article
- Ancestry-specific regulatory and disease architectures are likely due to cell-type-specific gene-by-environment interactions.medRxiv : the preprint server for health sciences · 2023Article
- The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis.Cellular & molecular immunology · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- MCL-1 Inhibitor S63845 Distinctively Affects Intramedullary and Extramedullary Hematopoiesis.Pharmaceutics · 2023Article
- Supplying the trip to antibody production-nutrients, signaling, and the programming of cellular metabolism in the mature B lineage.Cellular & molecular immunology · 2022Review
- Article
- Plasma cell biology: Foundations for targeted therapeutic development in transplantation.Immunological reviews · 2021Review
- Importance of Bcl-2-family proteins in murine hematopoietic progenitor and early B cells.Cell death & disease · 2021Article
- Transcript-Level Dysregulation ofCancers · 2021Article
- BCL-XL antagonism selectively reduces neutrophil life span within inflamed tissues without causing neutropenia.Blood advances · 2021Article
- Therapeutics Targeting the Core Apoptotic Machinery.Cancers · 2021Review
- Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition.Blood · 2021Article
- B-cell capacity for differentiation changes with age.Aging cell · 2021Article
- Phosphatase PP2A enhances MCL-1 protein half-life in multiple myeloma cells.Cell death & disease · 2021Article
- Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pro-survival BCL-2 family members protect cells from programmed cell death that can be induced by multiple internal or external cues. Within the haematopoietic lineages, the BCL-2 family members BCL-2, BCL-XL and MCL-1 are known to support cell survival but the individual and overlapping roles of these pro-survival BCL-2 proteins for the persistence of individual leukocyte subsets in vivo has not yet been determined. By combining inducible knockout mouse models with the BH3-mimetic compound ABT-737, which inhibits BCL-2, BCL-XL and BCL-W, we found that dependency on MCL-1, BCL-XL or BCL-2 expression changes during B-cell development. We show that BCL-XL expression promotes survival of immature B cells, expression of BCL-2 is important for survival of mature B cells and long-lived plasma cells (PC), and expression of MCL-1 is important for survival throughout B-cell development. These data were confirmed with novel highly specific BH3-mimetic compounds that target either BCL-2, BCL-XL or MCL-1. In addition, we observed that combined inhibition of these pro-survival proteins acts in concert to delete specific B-cell subsets. Reduced expression of MCL-1 further sensitized immature as well as transitional B cells and splenic PC to loss of BCL-XL expression. More markedly, loss of MCL-1 greatly sensitizes PC populations to BCL-2 inhibition using ABT-737, even though the total wild-type PC pool in the spleen is not significantly affected by this drug and the bone marrow (BM) PC population only slightly. Combined loss or inhibition of MCL-1 and BCL-2 reduced the numbers of established PC >100-fold within days. Our data suggest that combination treatment targeting these pro-survival proteins could be advantageous for treatment of antibody-mediated autoimmune diseases and B-cell malignancies.
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