The CSF1 receptor is activated by dimerization upon binding of its ligand CSF1 and is involved in macrophage development. Rearrangement of the CSF1R gene was first detected in an acute megakaryoblastic leukemia (AMKL) cell line generating the RBM6-CSF1R fusion gene. A MEF2D-CSF1R fusion gene was described in a patient with primary pre-B cell acute lymphoblastic leukemia (pre-B ALL). Both fusion proteins contain the intact kinase domain of CSF1R. Philadelphia chromosome-like ALL (Ph-like ALL) is a subgroup of B-cell precursor ALL and is associated with a high risk of treatment failure. SSBP2-CSF1R fusions were detected in some patients with Ph-like ALL. They result from either the balanced translocation t(5;5)(q14;q32) or the duplication dup(5)(q14q32). Expression of this fusion gene results in cytokine-independent growth and enhanced STAT5 activation which are inhibited by dasatinib in vitro. CSF1R signaling was also shown to be suppressed by the ABL1 kinase inhibitor imatinib. Hence, the detection of CSF1R rearrangements by FISH may help in selecting ALL patients eligible for treatment with CSF1R inhibitors.