| Title |
Epigenetic regulation and leukaemia – research of novel biological, molecular and therapeutic aspects / |
| Translation of Title |
Epigenetinis reguliavimas ir leukemija – naujų biologinių, molekulinių ir terapinių aspektų tyrimai. |
| Authors |
Valiulienė, Giedrė |
| Full Text |
|
| Pages |
56 |
| Keywords [eng] |
Acute promyelocytic leukaemia ; epigenetics ; histone modifications ; acetylation ; methylation. |
| Abstract [eng] |
Several thousands of people worldwide are being diagnosed with acute promyelocytic leukaemia (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 HDACi belinostat (PXD101), 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. Moreover, we have evaluated the effect of epigenetic therapy on histone modification changes in APL xenograftic mice tumours and tissues. Results obtained could be valuable for future APL epigenetic therapy clinical studies as well. |
| Dissertation Institution |
Vilniaus universitetas. |
| Type |
Summaries of doctoral thesis |
| Language |
English |
| Publication date |
2018 |
