SUPR
Epigenetic gene regulation in acute myeloid leukemia
Dnr:

sens2017523

Type:

SNIC SENS

Principal Investigator:

Sören Lehmann

Affiliation:

Uppsala universitet

Start Date:

2017-11-27

End Date:

2024-12-01

Primary Classification:

30202: Hematology

Webpage:

Allocation

  • Cygnus /proj at UPPMAX: 23500 GiB
  • Castor /proj at UPPMAX: 23500 GiB
  • Castor /proj/nobackup at UPPMAX: 8500 GiB
  • Cygnus /proj/nobackup at UPPMAX: 8500 GiB
  • Bianca at UPPMAX: 2 x 1000 core-h/month

Abstract

Acute myeloid leukemia (AML) it the most common type of acute leukemia. Despite recent advances in basic knowledge regarding the mechanisms of AML transformation, it is still unclear what drives AML development. Long non-coding RNAs have been implicated in basic cellular functions but have in tumor development. Still, the role of lncRNA for transformation to AML remains unclear and large studies of lncRNA in AML is lacking. We have performed RNA-Seq of 400 AML cases during 2015 at SciLifeLab and will investigate the role of differentially expressed lncRNA between AML samples and normal bone marrow samples. The studies includes a general characterization of lncRNA in a large AML cohort but also functional studies of differentially expressed lncRNA that may be implicated in AML transformation. In the cohort, we have also performed targeted DNA sequencing of recurrently mutated genes in AML and low-pass whole-genome sequencing which defines AML genetic subgroups based on mutations and copy number variations. We also have extensive clinical information on the patients from the Swedish Acute Leukemia Registry which gives the possibility to correlate sequencing data to treatment response and survival of the patients. This large AML cohort is unique in an international perspective with regard to its size and the fact that it is so extensively characterized molecularly and clinically. We also aim to perform ChIP-Seq for transcription factors and histone modifications to study integrated gene expression patterns in selected AML cases. The PI Sören Lehmann is new professor of Hematology at Uppsala University and has a background at Karolinska Institute and active researchers at KI.