Multimerin-1 (MMRN1) as Novel Adverse Marker in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
A partir d'échantillons prélevés sur 933 patients pédiatriques atteints d'une leucémie myéloïde aiguë et inclus dans deux essais cliniques, cette étude rétrospective suggère l'intérêt de mesurer l'expression du gène MMRN1 pour identifier les patients à risque de récidive
PURPOSE: Exploratory gene expression array analyses suggested multimerin-1 (MMRN1) to be a predictive biomarker in acute myeloid leukemia (AML). Following-up on these studies, we evaluated the role of MMRN1 expression as outcome predictor in 2 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 polymerase chain reaction 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 (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 (hazard ratio [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.
Clinical Cancer Research , résumé, 2015