TY - JOUR
T1 - Retinoic acid and arsenic trioxide sensitize acute promyelocytic leukemia cells to ER stress
AU - Masciarelli, S.
AU - Capuano, E.
AU - Ottone, T.
AU - Divona, M.
AU - De Panfilis, S.
AU - Banella, C.
AU - Noguera, N. I.
AU - Picardi, A.
AU - Fontemaggi, G.
AU - Blandino, G.
AU - Lo-Coco, F.
AU - Fazi, F.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity. Indeed, in the presence of ER stress, ATO efficiently induced apoptosis in RA-sensitive and RA-resistant APL cell lines, at doses ineffective in the absence of ER stress. Our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML.
AB - Retinoic acid (RA) in association with chemotherapy or with arsenic trioxide (ATO) results in high cure rates of acute promyelocytic leukemia (APL). We show that RA-induced differentiation of human leukemic cell lines and primary blasts dramatically increases their sensitivity to endoplasmic reticulum (ER) stress-inducing drugs at doses that are not toxic in the absence of RA. In addition, we demonstrate that the PERK pathway, triggered in response to ER stress, has a major protective role. Moreover, low amounts of pharmacologically induced ER stress are sufficient to strongly increase ATO toxicity. Indeed, in the presence of ER stress, ATO efficiently induced apoptosis in RA-sensitive and RA-resistant APL cell lines, at doses ineffective in the absence of ER stress. Our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML.
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U2 - 10.1038/leu.2017.231
DO - 10.1038/leu.2017.231
M3 - Article
AN - SCOPUS:85041653910
VL - 32
SP - 285
EP - 294
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 2
ER -