Title : Tipping the Noxa/Mcl-1 balance overcomes ABT-737 resistance in chronic lymphocytic leukemia.

Pub. Date : 2012 Jan 15

PMID : 22128299






6 Functional Relationships(s)
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1 Tipping the Noxa/Mcl-1 balance overcomes ABT-737 resistance in chronic lymphocytic leukemia. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
2 RESULTS: Upon CD40 stimulation patient-specific variations in ABT-737 sensitivity correlated with differences in levels of Mcl-1 and its antagonist Noxa. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
3 Knockdown of Noxa, as well as Mcl-1 overexpression, corroborated the importance of the Noxa/Mcl-1 ratio in determining the response to ABT-737. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
4 Knockdown of Noxa, as well as Mcl-1 overexpression, corroborated the importance of the Noxa/Mcl-1 ratio in determining the response to ABT-737. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
5 Interestingly, increasing the Noxa/Mcl-1 ratio, by decreasing Mcl-1 (dasatinib and roscovitine) or increasing Noxa levels (fludarabine and bortezomib), resulted in synergy with ABT-737. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens
6 CONCLUSIONS: Thus, the Noxa/Mcl-1 balance determines sensitivity to ABT-737 in CD40-stimulated CLL cells. 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid MCL1 apoptosis regulator, BCL2 family member Homo sapiens