Here, we show that MKX is absent in hematopoiesis and aberrantly activated in AML and MM, mimicking the picture for IRX2, IRX3 and IRX5 in AML and BCP-ALL, and staging a functional reenactment of the role played by the closely related homeobox gene IRX1 in early myeloid and B-cell development. The gene discussed is IRX5; the disease is acute lymphoblastic leukemia.