Multiple Myeloma, Waldenström's Macroglobulinemia, and Benign Monoclonal Gammopathy: Characteristics of The B Cell Clone, Immunoregulatory Cell Populations and Clinical Implications

Mellstedt, Håkan; Holm, G.; Björkholm, Magnus

doi:10.1016/s0065-230x(08)60018-4

Cited by 77 publications

(47 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this latter disease, evidence has been presented to suggest the maturation of Curr Prabl Surg, monoclonal lymphocytes into plasma cells. 173 In multiple myeloma, of course, the maturation is not associated with regression).…”

Section: Pathology Of Posttransplant Lymphoproliferative Disordermentioning

confidence: 99%

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Nalesnik

Makowka

Starzl

1988

Current Problems in Surgery

249

111

View full text Add to dashboard Cite

Section: Pathology Of Posttransplant Lymphoproliferative Disordermentioning

confidence: 99%

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Nalesnik

Makowka

Starzl

1988

Current Problems in Surgery

249

111

View full text Add to dashboard Cite

“…Although in WM the malignant cells are found primarily in bone marrow, 20% to 70% of blood mononuclear cells are malignant B cells. 1,2 Analyses of the V regions revealed that malignant cells in WM often express somatically mutated IgM. 3 Distribution of replacement (R) and silent (S) mutations suggests that the IgM in WM is derived from cells at a late stage of differentiation that have undergone antigenic selection in germinal centers but failed to coordinate somatic mutation and class switching.…”

Section: Introductionmentioning

confidence: 99%

Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor

Ćirić

VanKeulen

Rodriguez

et al. 2001

Blood

View full text Add to dashboard Cite

The course of clonal evolution of 2 related clones in the blood of a patient with Waldenstrom macroglobulinemia (WM) indicates the functional importance for the expression of the B-cell receptor for the survival of these malignant cells. Protein and nucleotide sequencing of the paraproteins' variable regions revealed 2 predominant V and 2 VH sequences, each set comprised in the ratio 1:1.5. The 2 VH sequences and 2 V sequences shared the same VDJ and VJ junctional sequences, respectively, indicating that 2 malignant clones had evolved from a common ancestor. This is the first report on intraclonal heterogeneity in WM. Comparison of the V and VH sequences with the closest matching known germline genes showed that they contained approximately 10 somatic mutations each. The distribution and type of mutations demonstrate that mutations have continued to accumulate in the malignant clones and that selection has been operating to preserve immunoglobulin structure. (Blood. 2001;97:321-323)

show abstract

“…The idiotypic Ig is a unique tumor antigen of B-cell malignancies, which may be presented as complete Ig molecules on the tumor cell surface (1) and as peptides in the groove of the MHC molecules (2). The tumor-derived idiotype may spontaneously elicit a humoral and cellular anti-idiotypic response (3), which may control the growth of the myeloma B-cell clone.…”

mentioning

confidence: 99%

Long-term Idiotype Vaccination Combined with Interleukin-12 (IL-12), or IL-12 and Granulocyte Macrophage Colony-Stimulating Factor, in Early-Stage Multiple Myeloma Patients

Hansson

Abdalla

Moshfegh

et al. 2007

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose and Experimental Design: Twenty-eight patients with immunoglobulin G myeloma stages I to II were immunized i.d. over 110 weeks with autologous M protein combined with interleukin-12 (IL-12; n = 15) or with IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF; n = 13). Idiotype-specific T-cell responses were assessed by [ 3 H]thymidine incorporation, enzyme-linked immunospot assay, and delayed-type hypersensitivity reaction. Results: Based on these three assays, idiotype-specific immune responses were noted in 5 of 15 (33%) patients in the IL-12 group and in 11 of 13 (85%) patients in the GM-CSF/IL-12 group (P < 0.01). Immune response was seen only in patients with M-component concentration of <50 g/L. Three of 16 (19%) responders showed a gradually increasing idiotype-specific T-cell response, whereas 11 of 16 (69%) patients showed initial response, which then disappeared rapidly; the latter pattern was frequently associated with subsequent progressive disease. Immune nonresponse was associated with an increase in the numbers of CD4 + /CD25 + cells (regulatory T cells), which was absent in responding patients. Median time to progression for immune responders (n = 16) was 108 weeks compared with 26 weeks for nonresponders (n = 12; P = 0.03). Conclusions: These results indicate that idiotype immunization of myeloma patients with GM-CSF and IL-12 may induce specific T-cell response more frequently than with IL-12 alone and that immune response may correlate with time to progression and nonresponse with increased numbers of regulatory T cells.

show abstract

Multiple Myeloma, Waldenström's Macroglobulinemia, and Benign Monoclonal Gammopathy: Characteristics of The B Cell Clone, Immunoregulatory Cell Populations and Clinical Implications

Cited by 77 publications

References 105 publications

The diagnosis and treatment of posttransplant lymphoproliferative disorders

The diagnosis and treatment of posttransplant lymphoproliferative disorders

Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor

Long-term Idiotype Vaccination Combined with Interleukin-12 (IL-12), or IL-12 and Granulocyte Macrophage Colony-Stimulating Factor, in Early-Stage Multiple Myeloma Patients

Contact Info

Product

Resources

About