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© Yang SI, Institut Pasteur
Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
18
Feb 2021
Status
Ongoing
Members
4
Structures
2

About

Rearranged Mixed Lineage lLukaemia (MLLr) is a form of leukaemia representing approximately 75% of paediatric acute leukaemia and 10% of adult leukaemia (AML and ALL), with a very poor prognosis of survival at 5 years (5-45%). In MLLr, lysine methyltransferase DOT1L becomes necessary for cell proliferation following translocations involving histone methyltransferase MLL. MLL loses its methyltransferase activity and, via partners, recruits DOT1L on its target genes, which are essential for the development of haematopoietic cells, but which become pro-leukemic when constitutively expressed. Thus, the inhibition of DOT1L activity is a promising therapeutic strategy for the treatment of MLL fusion-related leukaemia. The inhibitor EPZ5676 has entered phase I but results are limited due to poor pharmacological properties. We have synthesized a new DOT1L inhibitor that specifically inhibits the proliferation of MLL-r cells and shows very promising properties. We are optimising the compound by developing a new synthesis pathway, characterizing the biological activity in different MLL-r lines and developing a cell screening assay.

Funding: Ligue nationale contre le Cancer Comité Ile de France