IgM k multiple myeloma with monoclonal surface immunoglobulin expression

AbstractMonoclonal gammopathy of undetermined significance (MGUS) can transform to multiple myeloma (MM). In myeloma, mutated VHgenes with sequence homogeneity reveal a postfollicular origin. Previously, some MGUS cases showed mutated VH genes with intraclonal variation, indicating an earlier stage of arrest. We investigated progression from 2 of 2 MGUS to MM, in which VH genes confirmed clonal evolution. In one MGUS case, intraclonal heterogeneity was evident, and transformation to myeloma occurred rapidly with apparent homogeneity in the emergent clone. However, residual MGUS-derived sequences were detectable at this time. Heterogeneity in MGUS does not associate with benign disease, but it indicates an origin from a tumorigenic cell, most likely surface immunoglobulin+, undergoing somatic mutation. The remaining case displayed intraclonal homogeneity at the MGUS stage, conceivably resulting from a self-cloning outgrowth from MGUS with heterogeneity. Transformation can occur at either MGUS stage, but it involves a single cell in which somatic mutation is then silent.

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Immunobeads Test (Antibody Coated Polyacrylamide Beads) in the Immunological Characterization of Lymphoproliferative Disorders

The International Journal of Biological Markers ◽

10.1177/172460088700200307 ◽

1987 ◽

Vol 2 (3) ◽

pp. 173-176

Author(s):

Teodoro Chisesi ◽

Michele Vespignani ◽

Giovanni Capnist

Keyword(s):

Multiple Myeloma ◽

Chronic Lymphocytic Leukemia ◽

Normal Subjects ◽

Lymphoproliferative Disorders ◽

Lymphocytic Leukemia ◽

Immunological Characterization ◽

Surface Immunoglobulin ◽

Non Hodgkin Lymphoma ◽

Patient Groups

Three groups of patients with immunoproliferative disorders (15 multiple myeloma, 11 non-Hodgkin's lymphoma, 21 chronic lymphocytic leukemia) were studied by immunological characterization and compared to a group of 20 normal subjects (controls) using anti-immunoglobulin coated polyacrylamide beads (T-B Quantigen test, QT), erythrocyte rosettes (ER), surface immunoglobulin (SIg), and monoclonal antibodies for T and B cells (OKT3; OKT11; OKT8; OKT4; IaDR); null cells (NC) and double marker (DM) cells were also considered. The values for normal subjects for T-B, NC and DM cells were comparable. Results for the patient groups strikingly differed. There were progressively larger differences between the T and B percentages obtained with different techniques. The largest differences were seen in patients with chronic lymphocytic leukemia and the smallest in multiple myeloma patients; values were intermediate in non-Hodgkin lymphoma. The different findings were related to the number of DM cells (ER +, SIg+ QT+) and the different tests used. The importance of these findings in the diagnostic appproach to lymphoproliferative disorders is discussed.

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Multiple Myeloma with Monoclonal Surface Immunoglobulin Expression

Acta Cytologica ◽

10.1159/000333768 ◽

1996 ◽

Vol 40 (2) ◽

pp. 358-362

Author(s):

Cherie H. Dunphy ◽

Lorenzo M. Galindo ◽

William S. Velasquez

Keyword(s):

Multiple Myeloma ◽

Surface Immunoglobulin

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Proteasome inhibitors as therapeutics

Essays in Biochemistry ◽

10.1042/bse0410205 ◽

2005 ◽

Vol 41 ◽

pp. 205-218

Author(s):

Constantine S. Mitsiades ◽

Nicholas Mitsiades ◽

Teru Hideshima ◽

Paul G. Richardson ◽

Kenneth C. Anderson

Keyword(s):

Multiple Myeloma ◽

Drug Class ◽

Proteasome Inhibitors ◽

Cell Cycle Regulators ◽

Current State ◽

Intracellular Mechanism ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

Hodgkin's Lymphomas ◽

Clinical Research Data

The ubiquitin–proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas.

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