Evidence that the clonogenic cell in multiple myeloma originates from a pre-switched but somatically mutated B cell - PubMed (original) (raw)
Evidence that the clonogenic cell in multiple myeloma originates from a pre-switched but somatically mutated B cell
M H Bakkus et al. Br J Haematol. 1994 May.
Abstract
There is still much controversy about the precursor cell type in multiple myeloma (MM). Some authors claim that it is a pre-B cell, others state that it is a memory B cell or plasmablast. We have recently shown that the VDJ region of the MM immunoglobulin heavy chain gene is somatically hypermutated and antigen selected, without intraclonal variation or evolution in time. By using a patient-specific PCR approach we have now obtained evidence that the premyeloma cell can be situated in the pre-switched B-cell compartment and that heavy chain switching can occur without further somatic mutation. Based on the MM immunoglobulin sequences derived from the bone marrow, patient-specific CDR2 and CDR3 oligonucleotides were designed. B lymphocytes were separated from plasma cells based on the expression of CD19 and HLA class II or surface bound IgM using immunomagnetic beads. The expressed Ig sequences were amplified by RT-PCR using patient specific CDR2 primers and isotype specific primers (C mu, C gamma, and C alpha). Myeloma-specific Ig sequences were detected by a myeloma-specific CDR3 probe and sequenced. In one out of five cases we found in the peripheral blood clonally related IgM and IgA sequences with the same somatic mutations as the MM-IgG sequence. In another case of an IgG MM we found in the bone marrow clonally related IgA sequences with the same somatic mutations. These findings, together with the fact that myeloma-Ig genes contain somatic mutations without intraclonal variation, suggest that the clonogenic cell in multiple myeloma can originate from a pre-switched but somatically mutated B cell.
Similar articles
- Assessment of the role of clonogenic B lymphocytes in the pathogenesis of multiple myeloma.
Sahota S, Hamblin T, Oscier DG, Stevenson FK. Sahota S, et al. Leukemia. 1994 Aug;8(8):1285-9. Leukemia. 1994. PMID: 8057663 - Molecular characterization of IgA- and/or IgG-switched chronic lymphocytic leukemia B cells.
Matolcsy A, Casali P, Nádor RG, Liu YF, Knowles DM. Matolcsy A, et al. Blood. 1997 Mar 1;89(5):1732-9. Blood. 1997. PMID: 9057657 Free PMC article. - V(H) gene analysis of IgM-secreting myeloma indicates an origin from a memory cell undergoing isotype switch events.
Sahota SS, Garand R, Mahroof R, Smith A, Juge-Morineau N, Stevenson FK, Bataille R. Sahota SS, et al. Blood. 1999 Aug 1;94(3):1070-6. Blood. 1999. PMID: 10419900 - Multiple myeloma: new evidence and insights from the immunoglobulin heavy chain gene and phenotypes.
Takishita M, Kosaka M. Takishita M, et al. Leuk Lymphoma. 1995 Nov;19(5-6):395-400. doi: 10.3109/10428199509112196. Leuk Lymphoma. 1995. PMID: 8590838 Review. - Molecular analysis of immunoglobulin genes in multiple myeloma.
Kosmas C, Stamatopoulos K, Stavroyianni N, Belessi C, Viniou N, Yataganas X. Kosmas C, et al. Leuk Lymphoma. 1999 Apr;33(3-4):253-65. doi: 10.3109/10428199909058425. Leuk Lymphoma. 1999. PMID: 10221505 Review.
Cited by
- Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation.
Gong L, Qiu L, Hao M. Gong L, et al. Cancers (Basel). 2024 Jan 24;16(3):498. doi: 10.3390/cancers16030498. Cancers (Basel). 2024. PMID: 38339250 Free PMC article. Review. - Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing.
Kim M, Jeon K, Hutt K, Zlotnicki AM, Kim HJ, Lee J, Kim HS, Kang HJ, Lee YK. Kim M, et al. PLoS One. 2021 Jun 24;16(6):e0253541. doi: 10.1371/journal.pone.0253541. eCollection 2021. PLoS One. 2021. PMID: 34166440 Free PMC article. - The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma.
Giannakoulas N, Ntanasis-Stathopoulos I, Terpos E. Giannakoulas N, et al. Int J Mol Sci. 2021 Apr 24;22(9):4462. doi: 10.3390/ijms22094462. Int J Mol Sci. 2021. PMID: 33923357 Free PMC article. Review. - Definition of a multiple myeloma progenitor population in mice driven by enforced expression of XBP1s.
Kellner J, Wallace C, Liu B, Li Z. Kellner J, et al. JCI Insight. 2019 Apr 4;4(7):e124698. doi: 10.1172/jci.insight.124698. eCollection 2019 Apr 4. JCI Insight. 2019. PMID: 30944260 Free PMC article. - Myelomatous plasma cells display an aberrant gene expression pattern similar to that observed in normal memory B cells.
Báez A, Piruat JI, Caballero-Velázquez T, Sánchez-Abarca LI, Álvarez-Laderas I, Barbado MV, García-Guerrero E, Millán-Uclés Á, Martín-Sánchez J, Medrano M, Pérez-Simón JA. Báez A, et al. Am J Cancer Res. 2014 Dec 15;5(1):386-95. eCollection 2015. Am J Cancer Res. 2014. PMID: 25628947 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous