Analys av enskilda celler för precisionsmedicin vid akut barnleukemi

Tidsperiod: 2020-01-01 till 2023-12-31

Projektledare: Jessica Nordlund

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 6 000 000 SEK

The established chemotherapeutic treatment strategies used in pediatric oncology benefit groups of patients with similar clinical manifestations. Relapsed, chemorefractory, and extramedullary disease remain extremely difficult to treat and survivors of pediatric cancer suffer from toxic and other long-term side effects as a result of intensive chemotherapeutic treatment. Targeted treatments are necessary to address the needs of resistant and refractory disease and to replace nonspecific toxic chemotherapy, even in patients with chemosensitive disease.The aim of this project is to advance the understanding of the cellular composition of pediatric acute lymphoblastic leukemia (ALL) cells and the consequences for the molecular phenotypes of individual cells upon perturbation with different drugs.We will use state-of-the-art methods to generate single-cell transcriptional and epigenetic profiles in combination with ex vivo drug screening to detect potential new targeted drugs and to better understand the molecular phenotypes of cellular drug resistance. As central nervous system (CNS) relapse remains a serious complication in leukemia treatment, we will also compare the cellular phenotypes of matched bone marrow blasts with those isolated from the CNS. The proposed study addresses a largely previously unstudied aspect of pediatric leukemia, where the majority previous studies have been performed on bulk material, which does not allow for detection of rare cell types.