The Bcl-2 family member Bfl-1/A1 is strongly repressed in normal and malignant plasma cells but is a potent anti-apoptotic factor for myeloma cells
Open accessAbstract
Terminal B-cell differentiation is a multi-step process, from short-lived plasmablasts to mature long-lived plasma cells (PC). The anti-apoptotic Bcl-2 family member Bfl-1/A1 plays a critical role in the survival of mature B cells. However, its potential involvement at the later stages of B-cell development remains highly controversial. Our aim was thus to clarify the place of Bfl-1/A1 in the biology of normal PC and in the pathogenesis of multiple myeloma (MM), the major PC dyscrasia. Using gene expression profiling and quantifiable reverse transcription polymerase chain reaction experiments, we found a similar down-regulation of Bfl-1/A1 in both normal immature plasmablasts and mature PC when compared with B cells. In myeloma cells, the level of Bfl-1/A1 was low and Bfl-1/A1 was not a nuclear factor kappaB-inducible gene. Collectively, these data demonstrate that Bfl-1/A1 is not involved in the prolonged survival of normal mature PC, and that Bfl-1/A1 deregulation is not a common oncogenic event in MM. However, overexpression of Bfl-1/A1 by retroviral transduction promoted autonomous survival of an interleukin-6-dependent myeloma cell line and rendered it less sensitive to dexamethasone. Thus, Bfl-1/A1 transduction could be an interesting tool to obtain myeloma cell lines from primary samples and to favour the in vitro generation of antibody-secreting, long-lived normal PC.
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Aβ42-mediated upregulation occurred in expression of genes encoding cytokines IL-1β, CEX-1, TNF-α, COX-2, B94, and proapoptotic Bax and Bik proteins.
“These analyses indicated significant Aβ42-mediated upregulation in the expression of a family of genes encoding the cytokines IL-1β, CEX-1, and TNF-α, COX-2, B94, and the proapoptotic Bax and Bik proteins (Guo et al., 1998; Metcalfe et al., 2004; Tarte et al., 2004).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Tarte et al., 2004
Anti-apoptotic Bcl-2 family members such as Bfl-1(A1) play critical roles in the survival of aged and terminally differentiated cells and break the mechanistic link between inflammatory signaling and apoptosis.
“Anti-apoptotic Bcl-2 family members such as Bfl-1(A1) play critical roles in the survival of aged and terminally differentiated cells and break the mechanistic link between inflammatory signaling and apoptosis (Tarte et al., 2004).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Tarte et al., 2004
Cites
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 12,617 · see citing works
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S., Jagannath, S., Irwin, D., Rajkumar, S. V., Srkalovic, G., Alsina, M., Alexanian, R., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030288 · Cited by 2,632 · see citing works
Humoral Immunity Due to Long-Lived Plasma Cells
Slifka, M. K., Antia, R., Whitmire, J. K., & Ahmed, R. (1998) · Immunity · doi:10.1016/s1074-7613(00)80541-5 · Cited by 1,249 · see citing works
Shaffer, A. L., Lin, K., Kuo, T. C., Yu, X., Hurt, E. M., Rosenwald, A., Giltnane, J. M., Yang, L., Zhao, H., Calame, K. L., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00335-7 · Cited by 1,048 · see citing works
NF-κB as a Therapeutic Target in Multiple Myeloma
Hideshima, T., Chauhan, D., Richardson, P. G. G., Mitsiades, C. S., Mitsiades, N., Hayashi, T., Munshi, N. C., Dang, L., Castro, A. C., Palombella, V. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200360200 · Cited by 894 · see citing works
Shelef, M. A., Lin, K., McHeyzer‐Williams, L. J., Liao, J., McHeyzer‐Williams, M. G., & Calame, K. L. (2003) · Immunity · doi:10.1016/s1074-7613(03)00267-x · Cited by 839 · see citing works
Zong, W.-X., Edelstein, L., Chen, C.-L., Bash, J., & Gélinas, C. (1999) · Genes & Development · doi:10.1101/gad.13.4.382 · Cited by 738 · see citing works
Zhan, F., Hardin, J., Kordsmeier, B., Bumm, K., Zheng, M., Tian, E., Sanderson, R., Yang, Y., Wilson, C., Zangari, M., et al. (2002) · Blood · doi:10.1182/blood.v99.5.1745 · Cited by 688 · see citing works
Self-citationMoreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Rème, T., Lugagne, C., Moine, P., Rossi, J.-F., Klein, B., & Tarte, K. (2004) · Blood · doi:10.1182/blood-2003-06-1984 · Cited by 558 · see citing works
Self-citationLee, H. H., Dadgostar, H., Cheng, Q., Shu, J., & Cheng, G. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9136 · Cited by 522 · see citing works
Mitsiades, C. S., Mitsiades, N., Poulaki, V., Schlossman, R. L., Akiyama, M., Chauhan, D., Hideshima, T., Treon, S. P., Munshi, N. C., Richardson, P. G. G., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205664 · Cited by 463 · see citing works
Lin, K., Angelin‐Duclos, C., Kuo, T. C., & Calame, K. L. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4771-4780.2002 · Cited by 445 · see citing works
Derenne, S., Monia, B. P., Dean, N. M., Taylor, J. K., Rapp, M.-J., Harousseau, J., Bataille, R., & Amiot, M. (2002) · Blood · doi:10.1182/blood.v100.1.194 · Cited by 429 · see citing works
Grumont, R. J., Rourke, I. J., & Gerondakis, S. (1999) · Genes & Development · doi:10.1101/gad.13.4.400 · Cited by 403 · see citing works
Regulatory Mechanisms that Determine the Development and Function of Plasma Cells
Calame, K. L., Lin, K., & Tunyaplin, C. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141138 · Cited by 372 · see citing works
Hsu, S. Y., Kaipia, A. J., McGee, E. A., Lomeli, M. R., & Hsueh, A. J. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.23.12401 · Cited by 369 · see citing works
Biologic sequelae of nuclear factor–κB blockade in multiple myeloma: therapeutic applications
Mitsiades, N., Mitsiades, C. S., Poulaki, V., Chauhan, D., Richardson, P. G. G., Hideshima, T., Munshi, N. C., Treon, S. P., & Anderson, K. C. (2002) · Blood · doi:10.1182/blood.v99.11.4079 · Cited by 366 · see citing works
Commitment of B Lymphocytes to a Plasma Cell Fate Is Associated with Blimp-1 Expression In Vivo
Angelin‐Duclos, C., Cattoretti, G., Lin, K., & Calame, K. L. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.10.5462 · Cited by 337 · see citing works
Lin, E. Y., Orlofsky, A., Berger, M. S., & Prystowsky, M. B. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.4.1979 · Cited by 335 · see citing works
Pham, L. V., Tamayo, A. T., Yoshimura, L. C., Lo, P., & Ford, R. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.1.88 · Cited by 318 · see citing works
Medina, F., Segundo, C., Campos‐Caro, A., González-Garcı́a, I., & Brieva, J. A. (2002) · Blood · doi:10.1182/blood.v99.6.2154 · Cited by 286 · see citing works
Zhang, X., Gaillard, J., Robillard, N., Lu, Z., Gu, Z., Jourdan, M., Boiron, J.-M., Bataille, R., & Klein, B. (1994) · Blood · doi:10.1182/blood.v83.12.3654.3654 · Cited by 277 · see citing works
Self-citationHinz, M., Löser, P., Mathas, S., Krappmann, D., Dörken, B., & Scheidereit, C. (2001) · Blood · doi:10.1182/blood.v97.9.2798 · Cited by 259 · see citing works
Karsan, A., Yee, E., & Harlan, J. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27201 · Cited by 238 · see citing works
BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis
MOULDING, D. A., Akgul, C., Derouet, M. F., White, M., & Edwards, S. W. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.70.5.783 · Cited by 221 · see citing works
Piskurich, J. F., Lin, K., Lin, Y., et al. (2000) · Nature Immunology · doi:10.1038/82788 · Cited by 217 · see citing works
Tarte, K., Zhan, F., Vos, J. D., Klein, B., & Shaughnessy, J. D. (2003) · Blood · doi:10.1182/blood-2002-10-3161 · Cited by 215 · see citing works
Self-citationHumoral immunity and long-lived plasma cells
Manz, R. A., Arce, S., Cassese, G., Hauser, A. E., Hiepe, F., & Radbruch, A. (2002) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00356-4 · Cited by 210 · see citing works
Role of NF-κB in the Rescue of Multiple Myeloma Cells From Glucocorticoid-Induced Apoptosis by Bcl-2
Feinman, R., Koury, J., Thames, M., Barlogie, B., Epstein, J., & Siegel, D. S. D. (1999) · Blood · doi:10.1182/blood.v93.9.3044 · Cited by 200 · see citing works
Survival of leukemic B cells promoted by engagement of the antigen receptor
Bernal, A., Pastore, R. D., Asgari, Z., et al. (2001) · Blood · doi:10.1182/blood.v98.10.3050 · Cited by 195 · see citing works
Zhan, F., Tian, E., Bumm, K., Smith, R., Barlogie, B., & Shaughnessy, J. D. (2003) · Blood · doi:10.1182/blood-2002-06-1737 · Cited by 166 · see citing works
Self-citationWerner, A. B., de Vries, E., Tait, S. W. G., Bontjer, I., & Borst, J. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201469200 · Cited by 158 · see citing works
A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells
Jourdan, M., Veyrune, J., Vos, J. D., Redal, N., Couderc, G., & Klein, B. (2003) · Oncogene · doi:10.1038/sj.onc.1206423 · Cited by 150 · see citing works
Self-citationTarte, K., Vos, J. D., Thykjær, T., Zhan, F., Fiol, G., Costes, V., Reme, T. X., Legouffe, É., Rossi, J., Shaughnessy, J. D., et al. (2002) · Blood · doi:10.1182/blood.v100.4.1113.h81602001113_1113_1122 · Cited by 150 · see citing works
Self-citationTaraban, V. Y., Rowley, T. F., O'Brien, L., Chan, H. T. C., Haswell, L. E., Green, M. H. A., Tutt, A. L., Glennie, M. J., & Al‐Shamkhani, A. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200212)32:12 · Cited by 149 · see citing works
Jourdan, M., Vos, J. D., Mechti, N., & Klein, B. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400758 · Cited by 134 · see citing works
Self-citationMatyszak, M. K., Denis‐Donini, S., Citterio, S., Longhi, R., Granucci, F., & Ricciardi‐Castagnoli, P. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199910)29:10 · Cited by 114 · see citing works
Nieborowska-Skorska, M., Hoser, G., Kossev, P. M., Wasik, M. A., & Skórski, T. (2002) · Blood · doi:10.1182/blood.v99.12.4531 · Cited by 114 · see citing works
Lin, K., Lin, Y., & Calame, K. L. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.8684-8695.2000 · Cited by 103 · see citing works
Edelstein, L. C., Lagos, L., Simmons, M. J., Tirumalai, H., & Gélinas, C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.8.2749-2761.2003 · Cited by 89 · see citing works
Schliephake, D. E., & Schimpl, A. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260142 · Cited by 88 · see citing works
D’Sa-Eipper, C., & Chinnadurai, G. (1998) · Oncogene · doi:10.1038/sj.onc.1201851 · Cited by 73 · see citing works
Long-Lived B Cells Are Distinguished by Elevated Expression of A1
Tomayko, M. M., & Cancro, M. P. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.1.107 · Cited by 71 · see citing works
Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma
Borson, N. D., Lacy, M. Q., & Wettstein, P. J. (2002) · Blood · doi:10.1182/blood.v100.13.4629 · Cited by 54 · see citing works
A1 is a growth-permissive antiapoptotic factor mediating postactivation survival in T cells
Gonzalez, J., Orlofsky, A., & Prystowsky, M. B. (2003) · Blood · doi:10.1182/blood-2002-04-1229 · Cited by 53 · see citing works
The CD40-Inducible Bcl-2 Family Member A1 Protects B Cells from Antigen Receptor-Mediated Apoptosis
Craxton, A., Chuang, P. I., Shu, G. L., et al. (2000) · Cellular Immunology · doi:10.1006/cimm.2000.1616 · Cited by 49 · see citing works
A cellular model for myeloma cell growth and maturation based on an intraclonal CD45 hierarchy
Bataille, R., Robillard, N., Pellat‐Deceunynck, C., et al. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00039.x · Cited by 47 · see citing works
Phospholipase Cγ2 Provides Survival Signals via Bcl2 and A1 in Different Subpopulations of B Cells
Wen, R., Chen, Y., Xue, L., Schuman, J., Yang, S., Morris, S. W., & Wang, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307318200 · Cited by 41 · cited 2× · see citing works
“…long- lived normal PC. Keywords: plasma cells, Bfl-1/A1, apoptosis, myeloma, B-cell differentiation, gene expression profile. research paper ª 2004 Blackwell Publishing Ltd, British Journal of Haematology, 125, 373–382 doi:10.1111/j.1365-2141.2004.04908.x Shapiro-Shelef et al, 2003).”
BackgroundInfluentialIsolation, maturational level, and functional capacity of human colon lamina propria plasma cells
Medina, F. (2003) · Gut · doi:10.1136/gut.52.3.383 · Cited by 32 · see citing works
Human A1 expression in acute myeloid leukemia and its relationship to Bcl-2 expression
Moreb, J. S., & Zucali, J. R. (2001) · Blood · doi:10.1182/blood.v97.2.578 · Cited by 6 · see citing works
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Bazan, N. G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.09.003 · Cited by 148 · see citing works
Activation of the IL-6/JAK2/STAT3 pathway induces plasma cell mastitis in mice.
Liu, Y., Zhang, J., Zhou, Y.-H., Zhang, H.-M., Wang, K., Ren, Y., Jiang, Y.-N., Han, S.-P., He, J.-J., & Tang, X.-J. (2018) · Cytokine · doi:10.1016/j.cyto.2018.05.002 · Cited by 46 · see citing works
Park, J., Kim, M., Na, G., Jeon, I., Kwon, Y.-K., Kim, J.-H., Youn, H., & Koo, Y. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.08.002 · Cited by 26 · see citing works
- Authors
- Tarte, K., Jourdan, M., Veyrune, J. L., Berberich, I., Fiol, G., Redal, N., Shaughnessy, J., & Klein, B.
- Affiliations
- Inserm (FR)
- Hôpital Saint Eloi (FR)
- University of Würzburg (DE)
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Klein, Bernard
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2004-03-23
- Volume
- 125
- Issue
- 3
- Pages
- 373-382
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- PMC
- PMC2685897
- OpenAlex
- W2049017785
- Cited by
- 28
- References
- 51
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2014: 1 · 2013: 1
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- Bcl-2 family proteins, plasma cells, multiple myeloma, apoptosis, anti-apoptotic factors, plasmablasts, B cell differentiation, interleukin-6, dexamethasone sensitivity, retroviral transduction, myeloma cell lines, long-lived plasma cells
- MeSH terms
- Cells, Cultured, Dexamethasone, Humans, Multiple Myeloma, Neoplasm Proteins, Plasma Cells, Transduction, Genetic, Tumor Cells, Cultured, Down-Regulation, Minor Histocompatibility Antigens, Interleukin-6, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis
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