Pablo Meseguer, Rocío Del Amor, Valery Naranjo
MICIL: Multiple-Instance Class-Incremental Learning for skin cancer whole slide images
Artificial intelligence in medicine
gamma delta tcell receptorpositive acute lymphoblastic leukemia tall highrisk poorly characterized disease studied clinical features 200 pediatric tall compared prognosis 93 cases 1067 protocolmatched non tall genomic features defined transcriptome genome sequencing experimental modeling used examine mechanistic impacts genomic alterations therapeutic vulnerabilities identified high throughput drug screening cell lines xenografts tall children three extremely highrisk 5year eventfree survival 33 v 70 age 310 73 age 10 p 95 x 10 5 5year overall survival 49 v 78 age 310 81 age 10 p 0002 differences observed non tall tall age group enriched genomic alterations activating lmo2 activation inactivating stag2 inactivation stag2lmo2 mechanistically show inactivation stag2 profoundly perturbs chromatin organization altering enhancerpromoter looping resulting deregulation gene expression associated tcell differentiation drug screening showed resistance prednisolone consistent clinical slow treatment response identified vulnerability dna repair pathways arising stag2 inactivation efficaciously targeted polyadpribose polymerase parp inhibition synergism hdac inhibitors exvivo drug screening pdx cells validated efficacy parp inhibitors well potential targets including nelarabine tall children age three extremely highrisk enriched stag2lmo2 stag2 loss perturbs chromatin conformation differentiation stag2lmo2 sensitive parp inhibition data provide diagnostic therapeutic framework pediatric tall authors supported american lebanese syrian associated charities st jude childrens research hospital nci grants r35 ca197695 p50 ca021765 cgm henry schueler 419 foundation cgm st baldricks foundation robert j arceci innovation award cgm gabriella miller kids first x01hd100702 dtt cgm r03ca256550 dtt cgm f32 5f32ca254140 lm garwood postdoctoral fellowship hematological malignancies program st jude childrens research hospital comprehensive cancer center sk project supported national cancer institute national institutes health following award numbers u10ca180820 ug1ca189859 u24ca114766 u10ca180899 u10ca180866 u24ca196173 content solely responsibility authors necessarily represent official views national institutes health funding agencies directly involved design study gathering analysis interpretation data writing manuscript decision submit manuscript publication