Molecular analysis of leukemia mediated alternations in normal blood cell development .
Description: This project aims to investigate the tumor host interphase with the intention to understand how malignant cells modify normal blood cell production in Acute B-lymphoid Leukemia (B-ALL). The most prominent symptoms of lymphoid leukemia are anemia, bleedings and infection, all as a consequence of impaired production of normal blood cells. While it has been thought that this defect was mainly a direct consequence of tumor expansion resulting in displacement of normal stem cells in bone marrow, it is becoming increasingly clear that the tumor host interplay is more complex. Using a mouse model for B-ALL as well as analysis of data from patients, we intend to explore the impact of this malignancy on normal cells in the bone marrow. Using CRISPR-CAS9 technology we aim to resolve the molecular mechanisms by which the tumor cells influence production and maturation of normal cells in the bone marrow. Furthermore, as we have detected deregulated expression of a substantial number of cytokine genes in mouse as well as human leukemia cells, we intend to dissect transcription factor networks that may underly these abnormalities. By comparative analysis of RNA seq data from human B-ALL samples we hope to be able to identify subgroups of leukemias with unique cytokine expression patterns, information that may be explored for the development of precision medicine. We hope that these studies will increase our ability to detect, classify and handle the clinical manifestations of B-ALL.
Funder: Vetenskapsrådet
Amount: SEK 9,800,000
Funding type: research
Funder scheme: Project grant
Start date: 2021-12-01
End date: 2026-11-30
Investigator: Mikael Sigvardsson
Institution: Linköping University
Funded outputs count: 5
Funder award ID: 2021-02379
OpenAlex ID: G4459934317