The mTOR hyperactivation in B-ALL is strictly dependent on oncogenic drivers, such as BCR-ABL1 fusion gene, on kinases commonly found aberrant in B-ALL such as cytokine receptor-like factor 2 (CRLF2) or JAKs, on hyperactivated growth receptors as colony-stimulating factor 1 receptor (CSF1R) and on overexpressed fms-related tyrosine kinase 3 (FLT3) and IL7R. The gene discussed is CRLF2; the disease is precursor B-cell acute lymphoblastic leukemia.