Non-coding RNAs in childhood leukemia

Dnr:

SNIC 2017/7-50

Type:

SNAC Small

Principal Investigator:

Vasilios Zachariadis

Affiliation:

Karolinska Institutet

Start Date:

2017-03-10

End Date:

2018-04-01

Primary Classification:

30203: Cancer och onkologi

Webpage:

Allocation

Abstract

We aim to describe the molecular events underlying the development, disease progression and therapy response in childhood leukemia, with the purpose of improving diagnostics, treatment conditions and reveal new therapeutic targets. Specifically, we aim to functionally characterize novel long non-coding RNAs, their role in leukemia development, drug response and clinical outcome. Our initial analyses show that lncRNA expression alone can discriminate between ALL subtypes. The continued computational analysis is focused on integrating additional genomic data from the same samples (DNA copy number, DNA-methylation), functional data (in vitro drug sensitivity) and publicly available data (histone modifications, chromatin conformation, nascent transcription) to find candidates of regulatory importance. These candidates will be genetically manipulated in ALL cell lines and primary samples to detail their role in gene regulation, including interacting DNA regions and associated proteins, and how they may influence leukemogenesis, cell survival and death. By coupling our analyses of primary samples with outcome data from the NOPHO clinical registry, we will also be able to detail how expression of individual or sets of lncRNAs and coding genes are associated with response to treatment and overall survival.