Andrea Rzepiel1, Nóra Kutszegi1, Bálint Egyed1, András Gézsi2, Judit C. Sági2, Ágnes F. Semsei2, Gábor Nyírő 3,4, Gábor T. Kovács1, Csaba Szalai2,5, Dániel J. Erdélyi1
1 2nd Department of Pediatrics, Semmelweis University, Budapest;
2 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest;
3 Hereditary Endocrine Tumours Research Group, Hungarian Academy of Science and Semmelweis University, Budapest;
4 Molecular Medicine Research Group, Hungarian Academy of Science and Semmelweis University, Budapest;
5 Heim Pal Children Hospital, Budapest
Introduction: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. There are approximately 60 new ALL cases per year in Hungary.
Extracellular vesicles containing microRNAs are in great interest of scientific research. Their role is not fully understood, especially not in pediatric leukemia. Although, altered microRNA expression pattern is established in many malignant conditions.
Aims: The aim of this study was to identify a set of microRNAs associated with pediatric ALL and its genetic subgroups.
Methods: Platelet-free plasma samples were obtained from 16 newly diagnosed de novo and 5 relapsed pediatric acute lymphoblastic leukemia patients and 10 healthy controls. RNA isolation was carried out using Qiagen miRNeasy serum/plasma kit. Quantification of 46 candidate miRNAs was performed using Custom TaqMan Advanced Low Density miRNA Array Card.
Results: The expression of 19 microRNAs showed significant difference when comparing ALL and healthy control platelet-free plasma samples (p < 0.05). Hsa-miR-128-3p, hsa-miR-181b-5p and hsa-miR-222-3p elevated most significantly in ALL samples. No difference was found in microRNA levels of hyperdiploid, ETV6/RUNX1 fusion positive and normal karyotype ALL patients.
Conclusion: Based on the literature, the role of hsa-miR-128 and hsa-miR-181 family members is known in normal lymphopoiesis, which can explain the background of our findings. Tumor suppressor gene TP53 as a target of certain microRNAs such as hsa-miR-222 might take a part of the development of leukemia. Circulating microRNAs might serve as biomarkers for pediatric acute lymphoblastic leukemia.
Doctoral School: Clinical Medicine
Program: Clinical application of basic science results
Supervisor: Dániel Erdélyi