Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive.

Design And Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters.

Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets.

Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366649PMC
http://dx.doi.org/10.3324/haematol.2011.052852DOI Listing

Publication Analysis

Top Keywords

multiple myeloma
20
immunoglobulin repertoire
16
myeloma immunoglobulin
12
somatic hypermutation
8
hypermutation load
8
immunoglobulin
7
myeloma
6
multiple
5
repertoire
5
myeloma intra-disease
4

Similar Publications

Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.

View Article and Find Full Text PDF

Introduction: Mitochondria and angiogenesis play key roles in multiple myeloma (MM) development, but their interrelated genes affecting MM prognosis are under-studied.

Methods: We analyzed TCGA_MMRF and GSE4581 datasets to identify four genes - CCNB1, CDC25C, HSP90AA1, and PARP1 - that significantly correlate with MM prognosis, with high expression indicating poor outcomes.

Results: A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the latter showing better survival.

View Article and Find Full Text PDF

Background: Secondary acute lymphoblastic leukemia (sALL) is rare in patients diagnosed with antecedent multiple myeloma (MM). This study aimed to elucidate the clinical features and outcomes of patients with sALL after MM.

Methods: We conducted this population-based study using the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed patients with sALL following MM treatment at our institution.

View Article and Find Full Text PDF

Multiple myeloma (MM) represents a difficult-to-treat plasma cell malignancy and the second most common hematologic malignancy in adults, significantly impacting kidney function. The spectrum of kidney involvement in MM is broad, encompassing electrolyte imbalances, tubular injury, and even rare glomerular diseases. The evolution of MM treatment modalities has led to notable improvements in the long-term survival of patients experiencing kidney-related complications.

View Article and Find Full Text PDF

Background: Anti-CD38 monoclonal antibodies (mAbs) have significantly changed the multiple myeloma treatment landscape. This meta-analysis compared the efficacy and safety of anti-CD38 mAb-based therapy versus standard therapy in newly diagnosed multiple myeloma (NDMM) patients.

Methods: We performed a comprehensive literature search on PubMed, the Cochrane Database, and ClinicalTrials.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!