ABL-class kinase fusions and other JAK pathway alterations in Ph-like ALL. (A) JAK2 fusions are caused by translocations or interstitial deletions involving various 5′ fusion partners that lead to constitutive activation of the JAK2 3′ gene tyrosine kinase domain (striped bars). (B) Rearrangements of the EPOR gene with accompanying frameshift or stop codon mutations lead to overexpression of a truncated EPOR protein that lacks negative regulatory tyrosine (Y) residues (patterned box). Other JAK/STAT alterations (TYK2, IL7R, and TSLP) are caused by (C) translocations or (D) insertions, deletions, or missense mutations (black bar). (E) ABL-class (eg, ABL1, ABL2, CSF1R, and PDGFRB) kinase fusions occur via similar mechanisms as in panel A.