While pre-B-ALL clones often do not express a functional pre-BCR, oncogenic tyrosine kinases (e.g., BCR-ABL1) and mutations of components of the RAS or PI3K/AKT pathway can also mimic the survival and proliferation signals of a constitutively active pre-BCR (Figure 5) [1,2]. The gene discussed is BCR; the disease is acute lymphoblastic leukemia.