Using genomics to identify high-risk myeloma after autologous stem cell transplantation.
Multiple myeloma is a malignancy of antibody-secreting plasma cells that expand in the bone marrow. Although high-dose therapy/autologous stem cell transplantation has become the standard of care for patients with multiple myeloma, survival is highly variable and can range from a few years to >10 years after diagnosis. Application of high-throughput genomics on a large uniformly untreated cohort of patients has revealed that activation of 1 of the 3 cyclin D genes is a universal initiating event in this disease and that acquisition of abnormalities of chromosome 1 leads to activation of CKS1B, a regulator of p27Kip1 degradation. Synergy between cyclin D2 and CKS1B, but not cyclin D1 and CKS1B, may lead to early treatment failure.
Shaughnessy
John D
JD
Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA.
Barlogie
Bart
B
D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000378:metabolism; D015331:Cohort Studies; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D033581:Stem Cell Transplantation / Q000401:mortality; D014182:Transplantation, Autologous; D017211:Treatment Failure
D009363:Neoplasm Proteins