engleski

Arsenic trioxide and rapamycin in acute myeloid leukemia (AML): potential synergistic effects

Arsenic trioxide (As2O3) is used together with the differentiative agent all-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL), a subtype of AML. As2O3 has also shown some promising proapoptotic effects on other AML subtypes in vitro, but the used doses were potentially toxic in vivo. To test whether antiproliferative effects of lower doses of As2O3 could be enhanced by addition of mTOR inhibitor rapamycin, we incubated AML cell lines and primary samples isolated from peripheral blood of 4 representative patients (APL, de novo AML, relapsed AML, secondary AML) with As2O3, ATRA, rapamycin and their combination. After 96-hours incubation, rapamycin potentiated antiproliferative effects of lower doses of As2O3 in non-APL AML cell lines without affecting the expression of differentiation marker CD11b. As2O3 also reduced the viability of primary AML blasts, except in the case of secondary AML that was clinically shown to be refractory to chemotherapy. The reduction in cell number both in APL and non- APL samples was even greater when rapamycin or ATRA were added in combination with As2O3 which indicates that these agents might act in synergy. Presented results show that combination of As2O3 with rapamycin might have some therapeutic potential in non-APL AML.

arsenic trioxide; rapamycin; acute myeloid leukemia

nije evidentirano