1993
DOI: 10.1084/jem.178.3.1091
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Evidence for a bone marrow B cell transcribing malignant plasma cell VDJ joined to C mu sequence in immunoglobulin (IgG)- and IgA-secreting multiple myelomas.

Abstract: SummaryMultiple myeloma is a B cell malignancy characterized by the expansion of plasma cells producing monodonal immunoglobulins (Ig). It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate giving rise to the plasma cell donal expansion. Antigenic features and specific Ig gene rearrangement shared by B lymphocytes and myeloma ceils have supported this hypothesis. However, the existence of such a precursor is ba… Show more

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Cited by 108 publications
(52 citation statements)
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“…39 Thus, transformation occurs after somatic hypermutation, and the lack of subsequent mutation indicates that the malignant, clonal lymphocyte-plasma cell population has escaped the antigen selection process. Lymphocyte populations clonally related to myeloma cells undergo class switching, 30,31,36,41 indicating that transformation occurs prior to class switching and leaves intact either the switching mechanisms or a preprogrammed switch. The transformed population in myeloma thus appears to be restricted to the myelomatous plasma cells and clonally related, hypermutated, pre-switched B lymphocyte populations found in the bone marrow or periphery.…”
Section: Monoclonal Gammopathy and The Progression To Myelomamentioning
confidence: 99%
“…39 Thus, transformation occurs after somatic hypermutation, and the lack of subsequent mutation indicates that the malignant, clonal lymphocyte-plasma cell population has escaped the antigen selection process. Lymphocyte populations clonally related to myeloma cells undergo class switching, 30,31,36,41 indicating that transformation occurs prior to class switching and leaves intact either the switching mechanisms or a preprogrammed switch. The transformed population in myeloma thus appears to be restricted to the myelomatous plasma cells and clonally related, hypermutated, pre-switched B lymphocyte populations found in the bone marrow or periphery.…”
Section: Monoclonal Gammopathy and The Progression To Myelomamentioning
confidence: 99%
“…The application of an allelespecific oligonucleotide (ASO)-based PCR with ASO derived from the sequence of CDR3 analyzed in each case enabled the detection of a B cell population clonally related to the plasma cell tumor. [24][25][26] Using this strategy, it became feasible to demonstrate the existence of pre-switch /␦ isotype bearing B cells clonally identical to ␥ or ␣ isotype-bearing myeloma cells from the BM of the patients. Sorting of BM B cells into CD45 + and CD38 + populations resulted in lineage-specific expression of the clonally related RNA, with the C and C␦ isotypes expressed by the CD45 + and the C␥ or C␣ isotypes by the CD38 + population.…”
Section: Origin Of the Clonogenic MM Cellmentioning
confidence: 99%
“…[24][25][26] The only definite proof that B cells at various stages of development are clonally related derived from the analysis of their Ig rearrangements and, more precisely, the unique sequence of their VDJ junctions, which, in case of clonal relationship, should be identical. The application of an allelespecific oligonucleotide (ASO)-based PCR with ASO derived from the sequence of CDR3 analyzed in each case enabled the detection of a B cell population clonally related to the plasma cell tumor.…”
Section: Origin Of the Clonogenic MM Cellmentioning
confidence: 99%
“…In two patients, bone marrow and peripheral blood were evaluated for the presence of residual myeloma cells by PCR, using oligonucleotide primers and probes derived from the tumor-specific Ig heavy-chain gene sequences, as previously reported. 20,21 Progression-free survival (PFS) was measured from the date of remission achievement to the date of progression or last followup. Overall survival (OS) was measured from the date of diagnosis to the date of death or last follow-up.…”
Section: Clinical Evaluationmentioning
confidence: 99%