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Chronic Lymphocytic Leukemia

Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells

Leukemia volume 18, pages 41–47 (2004)Cite this article

Abstract

Bmf is a BH3-only Bcl-2 family member that is normally sequestered to myosin V motors by binding to the dynein light chain 2 (DLC2). Certain damage signals release Bmf, which then binds prosurvival Bcl-2 proteins and triggers apoptosis. Here, two novel isoforms of human Bmf, Bmf-II and Bmf-III, were identified and cloned from cDNA derived from B-chronic lymphocytic leukemia (B-CLL) cells. Bmf-II and Bmf-III were characterized as two splice variants, lacking the BH3 domain but retaining the DLC2 binding domain. Bmf (here called Bmf-I) expression in HeLa cells induced apoptosis and reduced colony formation in contrast to Bmf-II and Bmf-III, which had no effect on apoptosis and instead increased colony formation. While bmf-I mRNA was expressed in many cell types, expression was higher in B lymphoid cells and bmf-II and bmf-III were mainly detected in B-CLL and normal B cells. bmf-I mRNA was upregulated in normal and leukemic B cells, while bmf-III mRNA was downregulated only in B-CLL cells by serum deprivation. We show that Bmf is regulated by transcriptional activation and alternative splicing and conclude that the relative levels of Bmf isoforms may have a role in regulating growth and survival in B cells and leukemic B-CLL cells.

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Acknowledgements

This work was supported by funds from the Swedish Cancer Society, The Swedish Medical Association and the Karolinska Institutet, Sweden.

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Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden

    A A Morales, A Olsson, M Jondal & L M Osorio

  2. Departments of Hematology/Oncology, Karolinska Hospital, Stockholm, Sweden

    F Celsing & A Österborg

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  1. A A Morales
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  2. A Olsson
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  3. F Celsing
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  4. A Österborg
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  5. M Jondal
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Correspondence to L M Osorio.

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Morales, A., Olsson, A., Celsing, F. et al. Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells. Leukemia 18, 41–47 (2004). https://doi.org/10.1038/sj.leu.2403183

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