title: Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation.
abstract: The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3-8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0.003) and 13q (P = 0.039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0.02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18.5 vs. 25.7 months, P = 0.035). Likewise, a shorter overall survival (44.8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0.20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression.
authors.affiliation: Department of Laboratory Hematology, Toronto General Hospital, University Health Network, Toronto, Canada. hong.chang@uhn.on.ca
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Qi
authors.forename: Young
authors.initials: Y
authors.lastname: Trieu
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Jocelyn C
authors.initials: JC
authors.lastname: Reader
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
authors.forename: Donna
authors.initials: D
authors.lastname: Reece
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D005784:Gene Amplification; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C093090:CKS1B protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases