Given that KMT2A-R ALL cells do not express a (pre) B cell receptor on the surface, we propose that the mechanism of negative selection is induced independently of the B cell receptor in these cells and that DYRK1A downregulates the negative selection of KMT2A-R B-ALL, thereby facilitating rapid leukemia cell proliferation. The gene discussed is DYRK1A; the disease is leukemia.