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New treatment for acute leukemia

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FIMM researchers have demonstrated that a previously approved drug called idelalisib is a promising treatment option for leukemia patients with the t(1;19) translocation.

Fusion genes are hybrids formed from two separate genes by structural genomic rearrangements. They play an important role in tumorigenesis, and they are often found in leukemias and other types of cancer. A recurrent gene fusion called TCF3-PBX1 resulting from a translocation occurring between chromosomes 1 and 19 occurs in 3-5% of acute lymphoblastic leukemias. It triggers the clonal expansion of pre-B cells in the bone marrow thus leading to cancer.

Patients with this type of leukemia typically benefit from chemotherapy. However, many relapse and subsequently develop resistant disease with few effective treatment options.

The research team led by Group Leader Caroline Heckman utilized the drug resistance and sensitivity testing platform developed at FIMM to identify novel treatment options for tumors containing this specific fusion gene. The team tested how patient cells reacted to more than 300 approved and investigational cancer drugs.

The researchers noticed that the cells from a relapsed patient were especially sensitive to a small molecule inhibitor called idelalisib (Zydelig). This drug has been approved as a treatment for chronic lymphocytic leukemia and certain lymphomas. Based on earlier clinical trials, idelalisib is known to be relatively well tolerated due to its specific mechanism of action.

“Drug sensitivity testing allows us to identify opportunities to reposition existing drugs for the treatment of new indications. In this study, we successfully identified idelalisib to be highly effective against acute lymphoblastic leukemia with the t(1;19) translocation. We were also able to show that the t(1;19) translocation is mechanistically linked to the sensitivity to idelalisib. The TCF3-PBX1 fusion protein directly regulates expression of phosphatidylinositide 3-kinase delta (PIK3CD), which is the target of idelalisib,” says Samuli Eldfors, the first author of the publication.
The study was performed by researchers from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki University Hospital, Charité Hospital Berlin and Goethe University, Frankfurt.  The results of this study were published in the leading hematology journal, Leukemia, last week.

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