Can leukaemia be "stopped" before its onset? Mouse model proved feasible!

With the development of technology, it is possible to detect early cancer signals in healthy individuals, which also arouses people's interest in "cancer interception" Acute myeloid leukemia (AML) is a common hematological malignancy The disease is usually accompanied by clonal hematopoiesis or myelodysplastic syndrome and other precursor diseases If it turns malignant again, then it is certain to develop leukemia VTP-50469 In a new study, Dr Scott Armstrong, chairman of the Boston Children's cancer and blood disease center, found that by using a small molecule (vtp-50469) to interfere with the second malignant transformation, cancer could be "stopped" before AML Mouse experiments also confirmed the feasibility of this view The results were published in the journal Science DOI: 10.1126/science.aax5863 Vtp-50469 was inspired by Armstrong and his colleagues' early study of a rare, high-risk infant leukemia (MLL rearranged leukemia) On December 10, 2019, Armstrong team published a paper in the Journal of cancer cell, saying that it has synthesized an efficient, highly selective and oral inhibitor of menin MLL (vtp50469), which can induce specific chromatin change and root out disease in MLL rearrangement leukemia model DOI:https://doi.org/10.1016/j.ccell.2019.11.001 Specifically, the cell line with MLL rearrangement had a selective response to vtp50469 Vtp50469 separated menin from the protein complex and inhibited the chromatin occupation of MLL in some genes Loss of MLL binding leads to changes in gene expression, differentiation and apoptosis When vtp50469 was used, the patients with mll-r acute myeloid leukemia or mll-r acute lymphocytic leukemia (all) showed a significant reduction in leukemia burden After treatment, many mice implanted mll-r all remained disease-free for more than one year In the latest study, researchers found that in npm1c / Dnmt3a mutant knockin mice (AML model), myeloid progenitor cells proliferate and self renew for a period of time before leukaemia Oral administration of vtp-50469 can reverse the situation that the blood cells before malignant tumor stop proliferation, leukemia will not occur, and there is no obvious toxic effect "In a preventive environment, individuals at high risk of AML may benefit from targeted epigenetic therapy," Armstrong said reference material: [1] Could leukemia be stopped before it starts?