Proteomics analysis of childhood acute lymphoblastic leukemia cell lines reveals novel drug vulnerabilities

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and it has a 5-year survival rate of 85% for European children. But for subsets of patients who fail to respond to standard of care chemotherapeutics, treatment options are limited, and clinical prognosis is poor. To establish a platform and methodology to better characterize ALL subtypes and identify their pharmacologic vulnerabilities, we assembled a biobank of 49 readily available childhood ALL cell lines representing diverse immunotypes and genetic profiles. Using these cell lines, we performed comprehensive multi-omic analyses, providing proteomic, transcriptomic and pharmacoproteomic characterization of childhood ALL. We used this resource to characterize the functional impact of genetic fusions and cellular differentiation states on the proteome. Additionally, we identified a novel drug vulnerability in one of the ALL subtypes. Our results are provided as an interactive online data portal with navigable proteomics, transcriptomics, and drug sensitivity profiles.