The Effects of Epitranscriptomic Modifications on pediatric Acute Lymphoblastic Leukemia Stem Cells

NAISS 2023/22-259


NAISS Small Compute

Principal Investigator:

Indranil Sinha


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

10203: Bioinformatics (Computational Biology) (applications to be 10610)




Acute lymphoblastic leukemia (ALL) is the most prevalent hematological cancer in children younger than 14 years of age and despite progress in intensive chemotherapy, 20-25% of pediatric and over 50% of adult patients show resistance to therapy and relapse. We want to investigate the role epitranscriptomic modifications in T-cell acute lymphoblastic leukemia (T-ALL) cancer cell generation and maintenance using the requested whole transcriptome RNA sequencing dataset of T-ALL patients. While ADAR1-mediated RNA editing, RNA splicing and RNA methylation promote LSC generation in adult myeloid malignancies, it has not yet been extensively studied in pediatric or young adult ALL. Because of high relapse related mortality rates, there is a pressing unmet medical need to predict and prevent acute leukemia relapse in children and to define relevant exposures that promote LSC generation. For this study we will be comparing the 121 treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia samples from requested dataset. This study includes three sub-aims 1) RNA editing through the editase ADAR1, 2) genes involved in RNA methylation (such as METTL3, METTL14 etc) and 3) RNA splicing with emphasis on adhesion molecules.