Abstract
<div>Abstract<p><b>Purpose:</b> Exploratory gene expression array analyses suggested multimerin-1 (<i>MMRN1</i>) to be a predictive biomarker in acute myelogenous leukemia (AML). Following up on these studies, we evaluated the role of <i>MMRN1</i> expression as outcome predictor in two recent Children's Oncology Group trials.</p><p><b>Experimental Design:</b> We retrospectively quantified <i>MMRN1</i> expression in 183 participants of AAML03P1 and 750 participants of AAML0531 by reverse-transcriptase PCR and correlated expression levels with disease characteristics and clinical outcome.</p><p><b>Results:</b> In AAML03P1, the highest quartile of <i>MMRN1</i> expression (expression ≥0.5 relative to <i>β-glucuronidase</i>; <i>n</i> = 45) was associated with inferior event-free survival (EFS; <i>P</i> < 0.002) and higher relapse risk (<i>P</i> < 0.004). In AAML0531, in which we quantified <i>MMRN1</i> mRNA for validation, patients with relative <i>MMRN1</i> expression ≥0.5 (<i>n</i> = 160) less likely achieved remission (67% vs. 77%, <i>P</i> = 0.006), and more frequently had minimal residual disease (43% vs. 24%, <i>P</i> = 0.001) after one induction course. They had inferior overall survival (OS; 44% ± 9% vs. 69% ± 4% at 5 years; <i>P</i> < 0.001) and EFS (32% ± 8% vs. 54% ± 4% at 5 years; <i>P</i> < 0.001) and higher relapse risk (57% ± 10% vs. 35% ± 5% at 5 years; <i>P</i> < 0.001). These differences were partly attributable to the fact that patients with high <i>MMRN1</i> expression less likely had cytogenetic/molecular low-risk disease (<i>P</i> < 0.001) than those with low <i>MMRN1</i> expression. Nevertheless, after multivariable adjustment, high <i>MMRN1</i> expression remained statistically significantly associated with shorter OS (HR, 1.57; 95% confidence interval, 1.17–2.12; <i>P</i> = 0.003) and EFS (HR, 1.34; 1.04–1.73; <i>P</i> = 0.025), and higher relapse risk (HR, 1.40; 1.01–1.94; <i>P</i> = 0.044).</p><p><b>Conclusions:</b> Together, our studies identify <i>MMRN1</i> expression as a novel biomarker that may refine AML risk stratification. <i>Clin Cancer Res; 21(14); 3187–95. ©2015 AACR</i>.</p></div>
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
