Identification of a Novel microRNA Profile in Pediatric Cancer Patients treated with Anthracycline Chemotherapy.

Kelsie E Oatmen
Olga H Toro-Salazar
Kristine Hauser
Kia N Zellars
Kathryn C Mason
Kan Hor
Eileen Gillan
Caroline J Zeiss
Daniel M. Gatti, The Jackson Laboratory
Francis G Spinale


INTRODUCTION: Anthracycline chemotherapy (AC) is associated with decline in left ventricular ejection fraction (LVEF), yet mechanisms remain unclear. While changes in microRNAs (miRs) have been identified in adult cardiovascular disease, miR profiles in pediatric AC patients have not been well studied. The goal of this study was to examine miR profiles (unbiased array) in pediatric AC patients compared to age matched referent normal patients.

HYPOTHESIS: Pediatric AC patients will express a unique miR profile at initiation and completion of therapy related to LVEF.

METHODS: Serum was collected in pediatric patients (n=12, 10-22yrs) with newly diagnosed malignancy requiring AC within 24-48 hours following initiation of therapy (30-60 mg/m

RESULTS: LVEF fell from AC initiation at ~1yr following AC (64.28% ± 1.78% vs 57.53% ± 0.95% respectively, p=0.004). Of the 84 miRs profiled, significant shifts in 17 miRs occurred relative to referent normal (p ≤ 0.05). Moreover, the functional domain of miRs associated with myocardial differentiation and development fell over 3-fold at completion of AC (p ≤ 0.05). Lastly, 3 miRs were associated with the fall in LVEF (p ≤ 0.05).

CONCLUSIONS: This study demonstrated for the first time that changes in miR expression occurs in pediatric AC patients. These findings suggest that miRs are a potential strategy for early identification of AC patients susceptible to LV dysfunction.