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Using genomics to identify high-risk myeloma after autologous stem cell transplantation
John D Shaughnessy1, Bart Barlogie
1Donna 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.
Abstract:
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.
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