TY - JOUR
T1 - The survival impact of CKS1B gains or amplification is dependent on the background karyotype and TP53 deletion status in patients with myeloma
AU - Hao, Suyang
AU - Lu, Xinyan
AU - Gong, Zimu
AU - Bassett, Roland L.
AU - Hu, Shimin
AU - Konoplev, Sergej N.
AU - Tang, Guilin
AU - Li, Shaoying
AU - Xu, Jie
AU - Khanlari, Mahsa
AU - Lee, Hans C.
AU - Manasanch, Elisabet E.
AU - Weber, Donna M.
AU - Orlowski, Robert Z.
AU - Jeffrey Medeiros, L.
AU - Lin, Pei
N1 - Funding Information:
Acknowledgements We thank the technologists in the Clinical Cytogenetics Laboratory at The University of Texas MD Anderson Cancer Center for their contributions. PL designed the study; SHao, PL, XL, SHu, GT, SL, MK, and JX collected data and reviewed the paper; ZG, RLB, and SNK performed statistical analyses; SHao, PL, RZO, and LJM analyzed data and wrote the paper. HCL, EEM, or DMW provided clinical data and reviewed the paper. All authors approved the final version of the paper. We thank Madalena Nguyen for technical assistance with paper preparation. This project was supported in part by the NIH/NCI Cancer Center Support Grant (award number P30 CA016672) and used the Biostatistics Resource Group.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2021/2
Y1 - 2021/2
N2 - Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp on overall survival in the context of other genetic aberrations, such as TP53 deletion, FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included 132 myeloma patients with CKS1B gain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39–88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. “Double hit,” defined as CKS1B gain/amp coexisting with TP53 deletion, or “triple hit,” defined as double hit plus t(4;14)FGFR3-IGH or t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2–104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit with TP53 deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients with CKS1B gain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact of CKS1B gain/amp depends on the background karyotype and TP53 status.
AB - Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp on overall survival in the context of other genetic aberrations, such as TP53 deletion, FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included 132 myeloma patients with CKS1B gain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39–88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. “Double hit,” defined as CKS1B gain/amp coexisting with TP53 deletion, or “triple hit,” defined as double hit plus t(4;14)FGFR3-IGH or t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2–104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit with TP53 deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients with CKS1B gain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact of CKS1B gain/amp depends on the background karyotype and TP53 status.
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U2 - 10.1038/s41379-020-00669-7
DO - 10.1038/s41379-020-00669-7
M3 - Article
C2 - 32908255
AN - SCOPUS:85090463745
SN - 0893-3952
VL - 34
SP - 327
EP - 335
JO - Modern Pathology
JF - Modern Pathology
IS - 2
ER -