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74 - Multiple myeloma
- from Part 3.6 - Molecular pathology: lymphoma and leukemia
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- By W. Michael Kuehl, Cancer Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA, P. Leif Bergsagel, Division of Hematology-Oncology, Comprehensive Cancer Center, Mayo Clinic, Scottsdale, AZ, USA
- Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
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- Book:
- Molecular Oncology
- Published online:
- 05 February 2015
- Print publication:
- 19 December 2013, pp 799-808
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Summary
The term “multiple myeloma” was suggested by von Rustizky in 1873, when he identified multiple discrete bone marrow (myel-) tumors (-oma) during an autopsy. Multiple myeloma (MM) is an age-dependent monoclonal tumor of bone marrow (BM) plasma cells (PC), often with significant end-organ damage that can include lytic bone lesions, anemia, loss of kidney function, immunodeficiency, and amyloid deposits in various tissues. With a yearly incidence of 20 000 in the USA, it accounts for nearly 20% of deaths from hematopoietic malignancies and about 2% of all deaths from cancer. Despite recent therapeutic advances, MM continues as a mostly incurable disease, but with a median survival that has increased to more than six years (1–4).
Multiple myeloma is a plasmablast/plasma-cell tumor of post-germinal center B cells
Pre-germinal center (GC) B cells can generate short-lived PC that mostly remain in the primary lymphoid tissue (Figure 74.1). Post-GC B cells can generate plasmablasts (PBs) that have successfully completed multiple rounds of somatic hypermutation and antigen selection, followed by IgH switch recombination, with both B-cell-specific DNA modification processes having oncogenic potential (5). These PB typically migrate to the BM, where stromal cells facilitate terminal differentiation into long-lived PC (6,7). Despite an aberrant immunophenotype, MM tumor cells are similar to post-GC PB/long-lived PC, including strong BM dependence, extensive somatic mutation of Ig genes, and absence of IgM expression in all but 1% of tumors.
1 - DIAGNOSIS AND GENETIC CLASSIFICATION OF MULTIPLE MYELOMA
- Edited by S. Vincent Rajkumar, Robert A. Kyle
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- Book:
- Treatment of Multiple Myeloma and Related Disorders
- Published online:
- 11 July 2009
- Print publication:
- 27 October 2008, pp 1-17
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Summary
INTRODUCTION
In the past decade we have seen great advances in our understanding of the genetic abnormalities present in multiple myeloma (MM) cells, which is believed to be the culprit in the pathogenesis of this disease. This progress has been, in great part, facilitated by the advent of novel molecular genetic and cytogenetic techniques, as well as the unparalleled power available through the genomic revolution. Furthermore, the continued testing for many of these genetic aberrations in large cohorts of patients has allowed for an increasingly accurate description of oncogenomics using primary patient samples. The translation and testing of this basic knowledge in these patient cohorts has provided clinical relevance that truly spans from the bench to the bedside. While much progress has been made in the understanding of the disease, many questions remain, particularly those capable of addressing progression events from the benign stages and unraveling complex interactions supporting clonal survival and evolution. In this chapter we discuss the knowledge regarding a global overview of genetic aberrations of MM cells, primary genetic lesions, secondary genetic events, and, lastly, their clinical implications.
GLOBAL OVERVIEW OF MM GENETICS
At the top hierarchical level, human MM can be divided into two diseases: hyperdiploid MM (H-MM) and nonhyperdiploid MM (NH-MM). The dichotomy separation of MM into these two entities is appealing from the didactic perspective and is clearly substantiated by an extensive body of literature.