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Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance

AutorThiago, Leandro S.; Pérez-Andrés, Martin; Balanzategui, Ana; Sarasquete, María Eugenia; Paiva, Bruno; Jara-Acevedo, Maria; Bárcena, Paloma; Sánchez, Maria Luz; Almeida, Julia ; González, Marcos ; San Miguel, Jesús F. ; García-Sanz, Ramón; Orfao, Alberto
Fecha de publicación2014
EditorFerrata Storti Foundation
CitaciónHaematologica 99(1): 155-162 (2014)
ResumenThe B-cell compartment in which multiple myeloma stem cells reside remains unclear. We investigated the potential presence of mature, surface-membrane immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow plasma cells among different subsets of peripheral blood B cells from ten patients (7 with multiple myeloma and 3 with monoclonal gammopathies of undetermined significance). The presence of clonotypic immunoglobulin heavy chain gene rearrangements was determined in multiple highly-purified fractions of peripheral blood B-lymphocytes including surface-membrane IgM+ CD27- naïve B-lymphocytes, plus surface-membrane IgG+, IgA+ and IgM+ memory CD27+ B cells, and normal circulating plasma cells, in addition to (mono)clonal plasma cells, by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH gene of tumor plasma cells from individual patients. Our results showed systematic absence of clonotypic rearrangements in all the different B-cell subsets analyzed, including M-compo-nent isotype-matched memory B-lymphocytes, at frequencies <0.03 cells/mL (range: 0.0003-0.08 cells/mL); the only exception were the myeloma plasma cells detected and purified from the peripheral blood of four of the seven myeloma patients. These results indicate that circulating B cells from patients with multiple myeloma and monoclonal gammopathies of undetermined significance are usually devoid of clonotypic B cells while the presence of immunophenotypically aberrant myeloma plasma cells in peripheral blood of myeloma patients is a relatively frequent finding.
DescripciónThis is an open-access paper.
Versión del editorhttp://dx.doi.org/10.3324/haematol.2013.092817
URIhttp://hdl.handle.net/10261/134667
DOI10.3324/haematol.2013.092817
Identificadoresdoi: 10.3324/haematol.2013.092817
issn: 0390-6078
e-issn: 1592-8721
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