Research Project 3
Sensitizing AML cells to RAR and VDR ligands to prevent leukaemia relapse
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Sensitizing AML cells to vitamin A and D derivatives to prevent leukemia relapse
Acute myeloid leukemia (AML) is an aggressive blood cancer that mainly targets older adults. Although the majority of patients respond to standard chemotherapy, for most the disease returns and leads to their death. Therefore, effective prophylaxis against AML relapse is one of the unmet clinical needs. We have shown that plant polyphenols or similar approved drugs enhance the ability of vitamin A and D derivatives to induce maturation of AML cells towards normal cells. Furthermore, when applied after a chemotherapeutic drug, such combinations increased the killing of leukemia cells. These data indicate that a similar combinatorial treatment given to AML patients in remission may delay or even prevent the recurrence of the disease.
In this study, we will employ mouse models of leukemia relapse to develop a novel approach for recurrence-preventive therapy of AML using effective and safe combinations of new synthetic vitamin A and D derivatives and leukemia cell-sensitizing agents. The mechanisms of acion of such combinations will be determined using established human and mouse AML cell lines, as well as patient-derived leukemia cells.