XIAP represents a promising therapeutic target for relapsed/refractory ALL

ABSTRACT: Acute lymphoblastic leukemia (ALL) represents the most frequent malignancy in children and relapse/refractory (r/r) disease is difficult to treat, both in children and adults. In search for novel treatment options against r/r ALL, we studied inhibitor of apoptosis proteins (IAP) and Smac mimetics (SM). SM sensitized r/r ALL cells towards conventional chemotherapy, even upon resistance against SM alone. The combination of SM and chemotherapy induced cell death via caspases and PARP, but independent from cIAP-1/2, RIPK1, TNFα or NF-B. Instead, XIAP was identified to mediate SM effects. Molecular manipulation of XIAP in vivo using microRNA-30 flanked shRNA expression in cell lines and patient-derived xenograft (PDX) models of r/r ALL mimicked SM effects and intermediate XIAP knockdown sensit

SUBMITTER: Dr. Michela Carlet 

PROVIDER: S-SCDT-10_15252-EMMM_202114557 | biostudies-other |

REPOSITORIES: biostudies-other