Book contents
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- 68 Molecular pathology of lymphoma
- 69 The molecular basis of acute myeloid leukemia
- 70 Molecular oncology of acute promyelocytic leukemia (APL)
- 71 Acute lymphoblastic leukemia (ALL)
- 72 B-cell chronic lymphocytic leukemia
- 73 Chronic myeloid leukemia: imatinib and next-generation ABL inhibitors
- 74 Multiple myeloma
- 75 EMS: the 8p11 myeloproliferative syndrome
- 76 JAK2 and myeloproliferative neoplasms
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
74 - Multiple myeloma
from Part 3.6 - Molecular pathology: lymphoma and leukemia
Published online by Cambridge University Press: 05 February 2015
- Frontmatter
- Dedication
- Contents
- List of Contributors
- Preface
- Part 1.1 Analytical techniques: analysis of DNA
- Part 1.2 Analytical techniques: analysis of RNA
- Part 2.1 Molecular pathways underlying carcinogenesis: signal transduction
- Part 2.2 Molecular pathways underlying carcinogenesis: apoptosis
- Part 2.3 Molecular pathways underlying carcinogenesis: nuclear receptors
- Part 2.4 Molecular pathways underlying carcinogenesis: DNA repair
- Part 2.5 Molecular pathways underlying carcinogenesis: cell cycle
- Part 2.6 Molecular pathways underlying carcinogenesis: other pathways
- Part 3.1 Molecular pathology: carcinomas
- Part 3.2 Molecular pathology: cancers of the nervous system
- Part 3.3 Molecular pathology: cancers of the skin
- Part 3.4 Molecular pathology: endocrine cancers
- Part 3.5 Molecular pathology: adult sarcomas
- Part 3.6 Molecular pathology: lymphoma and leukemia
- 68 Molecular pathology of lymphoma
- 69 The molecular basis of acute myeloid leukemia
- 70 Molecular oncology of acute promyelocytic leukemia (APL)
- 71 Acute lymphoblastic leukemia (ALL)
- 72 B-cell chronic lymphocytic leukemia
- 73 Chronic myeloid leukemia: imatinib and next-generation ABL inhibitors
- 74 Multiple myeloma
- 75 EMS: the 8p11 myeloproliferative syndrome
- 76 JAK2 and myeloproliferative neoplasms
- Part 3.7 Molecular pathology: pediatric solid tumors
- Part 4 Pharmacologic targeting of oncogenic pathways
- Index
- References
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.
- Type
- Chapter
- Information
- Molecular OncologyCauses of Cancer and Targets for Treatment, pp. 799 - 808Publisher: Cambridge University PressPrint publication year: 2013