TY - JOUR
T1 - EZH2 Overexpression in Multiple Myeloma
T2 - Prognostic Value, Correlation With Clinical Characteristics, and Possible Mechanisms
AU - Goldsmith, Scott R.
AU - Fiala, Mark A.
AU - O'Neal, Julie
AU - Souroullas, George P.
AU - Toama, Wael
AU - Vij, Ravi
AU - Schroeder, Mark A.
N1 - Funding Information:
This study used the Multiple Myeloma Research Foundation (MMRF) CoMMpass Dataset. The interpretation and reporting of these data are the sole responsibility of the authors. S.R.G. would like to acknowledge the National Cancer Institute of the National Institutes of Health (grant number R25CA190190) for funding and the principal investigator Ramaswamy Govindan, MD, for protected research time. The authors acknowledge the efforts of the MMRF and the centers contributing to the CoMMpass study.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/11
Y1 - 2019/11
N2 - Background: EZH2 is a histone methyltransferase that suppresses genes involved in cell cycle control. Overexpression of EZH2 has been associated with a poor prognosis in various malignancies. Pawlyn et al recently reported poor outcomes in patients with multiple myeloma and overexpression of EZH2. In order to validate these findings, we analyzed EZH2 expression and outcomes among patients from the CoMMpass study. Patients and Methods: We extracted clinical, expression, and genomic data from Interim Analysis 13 of the MMRF CoMMpass study, which harbors data from over 1000 patients with multiple myeloma. Correlations were drawn between EZH2 expression and common genetic mutations. We analyzed the association of EZH2 overexpression with progression-free (PFS) and overall survival (OS). Results: The estimated median PFS for patients with EZH2 overexpression was 20.2 months (95% confidence interval [CI], 16.3-25.5 months) compared with 37.2 months (95% CI, 31.5-40.7 months) for patients without (P <.001). The estimated median OS for patients with EZH2 overexpression was 52.3 months (95% CI, 38.5 months to unable to quantitate), whereas the median OS had not been reached for those without (P <.001). EZH2 overexpression was more common in those with 17p and 1q deletions, TP53 missense mutations, and certain KRAS mutations. Coinciding BRAF and EZH2 amplification occurred frequently. Conclusion: EZH2 overexpression is associated with worse outcomes among patients with multiple myeloma from the CoMMpass study. Its known association with p53 and other drivers of malignancy support further lab-based and clinical study in multiple myeloma.
AB - Background: EZH2 is a histone methyltransferase that suppresses genes involved in cell cycle control. Overexpression of EZH2 has been associated with a poor prognosis in various malignancies. Pawlyn et al recently reported poor outcomes in patients with multiple myeloma and overexpression of EZH2. In order to validate these findings, we analyzed EZH2 expression and outcomes among patients from the CoMMpass study. Patients and Methods: We extracted clinical, expression, and genomic data from Interim Analysis 13 of the MMRF CoMMpass study, which harbors data from over 1000 patients with multiple myeloma. Correlations were drawn between EZH2 expression and common genetic mutations. We analyzed the association of EZH2 overexpression with progression-free (PFS) and overall survival (OS). Results: The estimated median PFS for patients with EZH2 overexpression was 20.2 months (95% confidence interval [CI], 16.3-25.5 months) compared with 37.2 months (95% CI, 31.5-40.7 months) for patients without (P <.001). The estimated median OS for patients with EZH2 overexpression was 52.3 months (95% CI, 38.5 months to unable to quantitate), whereas the median OS had not been reached for those without (P <.001). EZH2 overexpression was more common in those with 17p and 1q deletions, TP53 missense mutations, and certain KRAS mutations. Coinciding BRAF and EZH2 amplification occurred frequently. Conclusion: EZH2 overexpression is associated with worse outcomes among patients with multiple myeloma from the CoMMpass study. Its known association with p53 and other drivers of malignancy support further lab-based and clinical study in multiple myeloma.
KW - CoMMpass study
KW - Epigenetics
KW - Prognosis
KW - Real-world
UR - http://www.scopus.com/inward/record.url?scp=85072538908&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2019.08.010
DO - 10.1016/j.clml.2019.08.010
M3 - Article
C2 - 31551170
AN - SCOPUS:85072538908
SN - 2152-2650
VL - 19
SP - 744
EP - 750
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 11
ER -