Among Ph-like ALL, the largest class of kinase-activating alterations is characterized by the deregulation/activation of JAK/STAT signaling due to different genetic alterations, including CRLF2 rearrangements (CRLF2r) with frequent JAK2 or JAK1 co-mutation, JAK2 rearrangements, EPOR rearrangements, SH2B3 deletions, and IL7R indels [18]. The gene discussed is SH2B3; the disease is acute lymphoblastic leukemia.