Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myeloma

P. Leif Bergsagel, W. Michael Kuehl

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations


Multiple myeloma (MM) is a tumor of long-lived bone marrow plasma cells (PCs). Nearly 40% of MM tumors have immunoglobulin H (IgH) translocations involving four recurrent chromosomal loci (oncogenes): 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (MMSET and FGFR3), and 16q23 (c-maf). Other MM tumors have Ig translocations revolving different loci, none of which is revolved in more than 1% of tumors. At least 25% of MM tumors have no Ig translocation. Unlike normal PCs, MM tumors usually express one of the three cyclin D genes at a high level. Translocations revolving 4p16 and 16q23 do not directly target a cyclin D gene, but they are associated with a high level of cyclin D2 expression. Although cyclin D1 is not expressed in normal hematopoietic cells, one-third of MM tumors ectopically express cyclin D1 in the absence of t(11;14). Despite a low proliferation index in MM, dysregulation of a cyclin D gene seems to be a unifying oncogenic event. Analysis of 34 MM cell Lines indicates that tumors having an IgH translocation are significantly over-represented, whereas tumors that ectopically express cyclin D1 are not represented. We speculate that ectopic cyclin D1 expression without t(11;14) is dependent on tumor-specific interaction with bone marrow stromal cells.

Original languageEnglish (US)
Pages (from-to)96-104
Number of pages9
JournalImmunological Reviews
StatePublished - Aug 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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