Display Settings:

Format

Send to:

Choose Destination
Blood. 2005 Jul 1;106(1):296-303. Epub 2005 Mar 8.

Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma.

Author information

  • 1Mayo Clinic Scottsdale, Comprehensive Cancer Center and Division of Hematology-Oncology, Scottsdale, AZ, USA. bergsagel.p@mayo.edu <bergsagel.p@mayo.edu>

Abstract

Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiploid pathway associated with a high prevalence of IgH translocations and a hyperdiploid pathway associated with multiple trisomies of 8 chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Biallelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify 5 recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into 8 TC (translocation/cyclin D) groups (11q13, 6p21, 4p16, maf, D1, D1+D2, D2, and none) that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor.

PMID:
15755896
[PubMed - indexed for MEDLINE]
PMCID:
PMC1895118
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk