Multimerin-1 (MMRN1) as Novel Adverse Marker in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group.

Abstract

PURPOSE:

Exploratory gene expression array analyses suggested multimerin-1 (MMRN1) to be a predictive biomarker in acute myelogenous leukemia (AML). Following up on these studies, we evaluated the role of MMRN1 expression as outcome predictor in two recent Children's Oncology Group trials.

EXPERIMENTAL DESIGN:

We retrospectively quantified MMRN1 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.

RESULTS:

In AAML03P1, the highest quartile of MMRN1 expression (expression ≥0.5 relative to β-glucuronidase; n = 45) was associated with inferior event-free survival (EFS; P < 0.002) and higher relapse risk (P < 0.004). In AAML0531, in which we quantified MMRN1 mRNA for validation, patients with relative MMRN1 expression ≥0.5 (n = 160) less likely achieved remission (67% vs. 77%, P = 0.006), and more frequently had minimal residual disease (43% vs. 24%, P = 0.001) after one induction course. They had inferior overall survival (OS; 44% ± 9% vs. 69% ± 4% at 5 years; P < 0.001) and EFS (32% ± 8% vs. 54% ± 4% at 5 years; P < 0.001) and higher relapse risk (57% ± 10% vs. 35% ± 5% at 5 years; P < 0.001). These differences were partly attributable to the fact that patients with high MMRN1 expression less likely had cytogenetic/molecular low-risk disease (P < 0.001) than those with low MMRN1 expression. Nevertheless, after multivariable adjustment, high MMRN1 expression remained statistically significantly associated with shorter OS (HR, 1.57; 95% confidence interval, 1.17-2.12; P = 0.003) and EFS (HR, 1.34; 1.04-1.73; P = 0.025), and higher relapse risk (HR, 1.40; 1.01-1.94; P = 0.044).

CONCLUSIONS:

Together, our studies identify MMRN1 expression as a novel biomarker that may refine AML risk stratification.

• Authors: George S Laszlo, Todd A Alonzo, Chelsea J Gudgeon, Kimberly H Harrington, Robert B Gerbing, Yi-Cheng Wang, Rhonda E Ries, Susana C Raimondi, Betsy A Hirsch, Alan S Gamis, Soheil Meshinchi, Roland B Walter
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 14 Pg. 3187-95 (Jul 15 2015) ISSN: 1557-3265 [Electronic] United States
• PMID: 25825478 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Blood Proteins
• multimerin

Topics

• Adolescent
• Biomarkers, Tumor (analysis)
• Blood Proteins (analysis, biosynthesis)
• Child
• Child, Preschool
• Clinical Trials, Phase III as Topic
• Disease-Free Survival
• Female
• Flow Cytometry
• Humans
• Infant
• Kaplan-Meier Estimate
• Leukemia, Myeloid, Acute (mortality, pathology)
• Male
• Multicenter Studies as Topic
• Prognosis
• Proportional Hazards Models
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Young Adult