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B Methods: b Patients with LSFL, grade 1-3a were randomised (1:1) to either involved-field radiotherapy alone (IFRT) (30-36Gy) or to CMT consisting of identical IFRT followed by 6 cycles of CVP. B Introduction: b The TROG99.03 represents the only randomised phase III trial of combined modality therapy (CMT) in limited-stage follicular lymphoma "LSFL", reporting a prolonged progression-free survival (PFS) in the CMT arm (MacManus, I JCO i , 2018). RITUXIMAB-CONTAINING COMBINED MODALITY THERAPY IN LIMITED STAGE FOLLICULAR LYMPHOMA: MATURE FOLLOW UP AND DERIVATION OF A NOVEL PROGNOSTIC SCORE FROM THE TROG99.03 TRIAL. [Extracted from the article]

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-κB. 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-sensitized r/r ALL cells towards chemotherapy-induced apoptosis. Interestingly, upon strong XIAP knockdown, PDX r/r ALL cells were outcompeted in vivo, even in the absence of chemotherapy. Our results indicate a yet unknown essential function of XIAP in r/r ALL and reveal XIAP as a promising therapeutic target for r/r ALL., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)