SC-B610: Novel markers of children receiving anthracycline therapy
What is the goal of the study?
Anthracycline related cardiotoxicity is a significant cause of morbidity and mortality in childhood cancer survivors, with cardiac events comprising the most common non-malignant cause of death in this population. Early biomarkers predictive of clinically significant cardiotoxicity are critical to the development of intervention strategies able to ameliorate or prevent progressive cardiac dysfunction. To this end, microRNAs (miRNAs), posttranscriptional regulators of gene expression, are gaining recognition for their role as important modulators and robust biomarkers of heart disease in the general population. Preliminary data from our group reveal that two miRNAs, miRs-29b and -499, are upregulated in the plasma of children receiving anthracycline chemotherapy and correlatewith anthracycline-associated troponin elevations. In this research study we will further elucidate the ability of miRs-29b and -499 to identify anthracycline-associated cardiac injury by defining their relationship with other predictors of cardiotoxicity in a larger cohort of children. First, we will examine the relationship between anthracycline-induced plasma miRNA upregulation and cumulative anthracycline dose. Given that the most important predictor of anthracycline-related heart failure has consistently been cumulative anthracycline dose, a significant correlation between miRNA expression and cumulative dose would provide strong supporting evidence that differential miRNA levels reflect the degree of anthracycline-induced cardiac injury. Next, we will determine the relationship between plasma miRs-29b and -499 upregulation and reduction in left ventricular strain at the end of anthracycline therapy. Increasing evidence demonstrates that early anthracycline-induced alterations in myocardial deformation, as assessed by tissue Doppler-based strain imaging or speckle tracking echocardiography, precede reductions in left ventricular ejection or shortening fractions. Reduced peak systolic global longitudinal strain (GLS) has been shown to be predictive of subsequent cardiomyopathy (ventricular dysfunction) in adults receiving anthracycline. Thus, correlation between plasma miRNA expression and GLS would not only support miRNA as a marker of acute myocardial injury, but may also support their potential role as predictors of anthracycline-induced cardiomyopathy. To accomplish these aims, we will recruit a prospective cohort of children receiving chemotherapy at Seattle Children?s Hospital, and combine that cohort with de-identified data and blood samples from a previously recruited cohort of similar children enrolled at UT Southwestern in Dallas. Expression, imaging, and clinical data of the two cohorts will be merged for the final analysis.
Who can participate in the study?
Please contact the study team listed below to learn more.