ABSTRACT: EPIGENETIC REGULATION AND LEUKEMIA – RESEARCH OF NOVEL BIOLOGICAL, MOLECULAR AND THERAPEUTIC ASPECTS

We would like to present the abstract of our keynote speaker – Giedrė Valiulienė – who is a Biochemistry PhD student, working in the Department of Molecular Cell Biology at Vilnius University Life Sciences Center.

Several thousands of people worldwide are being diagnosed with acute promyelocytic leukemia (APL) annually. Usually APL patients are being treated with anthracyclines and RA (all trans retinoic acid) combination. It has been showed that RA is able to induce APL cell differentiation into mature granulocytes. However, despite the general success of RA therapy, RA treatment resistant cases still remain a serious issue. It has been demonstrated that epigenetic remodelling could overcome APL resistance to RA. Moreover, it is known that limited efficacy of RA treatment in other types of leukemias does also rely largely on epigenetic factors.

In this study we aimed to evaluate the impact of epigenetic regulation of human APL cells induced to granulocytic differentiation. We have shown that histone deacetylase inhibitor (HDACi) belinostat (PXD101), and histone methyltransferase inhibitors (HMTi) BIX-01294 and 3-deazaneplanocine A facilitate RA-induced human APL cell NB4 and HL-60 differentiation into mature granulocytes. Results obtained support the efficacy of APL epigenetic therapy in vitro. In addition, we developed the murine APL xenograft model and showed that used agents prolong APL xenograftic mice life span and protect them against tumour formation. Furthermore, we have evaluated the effect of epigenetic therapy on histone modification changes in APL xenograftic mice tumours and tissues. Results obtained in our study could be valuable for future APL epigenetic therapy clinical studies as well.