Journal of Blood Disorders & Transfusion

Reframing the multiple myeloma stem cell hypothesis

2^nd International Conference on Hematology & Blood Disorders

September 29-October 01, 2014 DoubleTree by Hilton Baltimore-BWI Airport, USA

Leandro de Souza Thiago, Martin Perez-Andres, Bruno Paiva, Jesus F San Miguel and Alberto Orfao

Accepted Abstracts: J Blood Disorders Transf

Abstract:

The B-cell compartment where the multiple myeloma (MM) stem cell resides remains unclear. For more than a decade, it has been generally accepted that a less differentiated B-cell is responsible for the outgrowth of the more differentiated monoclonal plasma cell (M-PC) compartment. In line with this hypothesis, circulating peripheral blood (PB) CD19+ B-lymphocytes clonally identical to bone marrow (BM) M-PC have been recurrently detected in MM. In contrast, analysis of the engraftment of PB B-cells from MM patients into immunodeficient mice has provided inconsistent findings. Also, depletion of B-cells by rituximab therapy has shown no clear beneficial clinical effect in MM. Our group has investigated the potential presence of mature surface-membrane immunoglobulin (SmIg) + B lymphocytes clonally-related to the M-PC in different subsets of PB B-cells from 10 patients. Presence of clonotypic immunoglobulin heavy chain gene rearrangements was investigated in multiple highly-purified fractions of PB B-lymphocytes including SmIgM + CD27- na?ve B-lymphocytes, plus SmIgG + , SmIgA + and SmIgM + memory CD27 + B-cells, and normal circulating PC (N-PC), in addition to M-PC by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the clonal CDR3 sequence of M-PC from individual patients. Our results showed systematic absence of clonotypic rearrangements in all B-cell subsets analyzed, at frequencies ≤0.03 cells/μL; except for the M-PC compartment. In summary, our data show that clonotypic B-cells are undetectable in PB outside the compartment of M-PC, suggesting that the MM stem cell could more likely be related to the M-PC rather than to less differentiated na?ve and memory B-lymphocytes.

Biography :

Leandro de Souza Thiago has completed his PhD at the age of 26 years from Federal University of Rio de Janeiro and Postdoctoral training from Universidad de Salamanca, Spain. He is immunologist at the Brazilian National Cancer Institute (INCa) and full member of the Brazilian Working Group of Flow Cytometry (GBCFLUX). He has devoted his scientific career in order to understand the natural history of neoplasias and to improve cancer diagnosis.