Early genetic events provide the basis for a clinical classification of multiple myeloma.

W. Michael Kuehl, Peter Leif Bergsagel

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells that accumulate in the bone marrow leading to bone destruction and bone marrow failure. The germinal center processes of somatic hypermutation and switch recombination are implicated in the development of recurrent immunoglobulin gene translocations in 40% of patients. These affect five loci: 11q13, 6p21, 4p16, 16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and MAFB respectively. The remaining 60% of patients can be divided into four groups based on their expression of CCND1 and CCND2. The largest group (40%) ectopically express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC) groups identify patients with different genetics, biology, clinical features, prognosis and response to therapy.

Original languageEnglish (US)
Pages (from-to)346-352
Number of pages7
JournalHematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
StatePublished - 2005
Externally publishedYes

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Multiple Myeloma
Bone Marrow
Cyclin D
Chromosomes, Human, Pair 5
Immunoglobulin Genes
Chromosomes, Human, Pair 3
Polyploidy
Germinal Center
Trisomy
Plasma Cells
Genetic Recombination
Bone and Bones
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "Multiple myeloma is a tumor of somatically mutated, isotype-switched plasma cells that accumulate in the bone marrow leading to bone destruction and bone marrow failure. The germinal center processes of somatic hypermutation and switch recombination are implicated in the development of recurrent immunoglobulin gene translocations in 40{\%} of patients. These affect five loci: 11q13, 6p21, 4p16, 16q23 and 20q11, leading to dysregulation of CCND1, CCND2, FGFR3/MMSET, c-MAF and MAFB respectively. The remaining 60{\%} of patients can be divided into four groups based on their expression of CCND1 and CCND2. The largest group (40{\%}) ectopically express CCND1 bi-allelically and have hyperdiploidy with multiple trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19 and 21. The translocation and cyclin D (TC) groups identify patients with different genetics, biology, clinical features, prognosis and response to therapy.",
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