The expression of CALM/AF10 leads to the development of leukemia in murine bone marrow transplantation and transgenic models [9–12], and increasing evidence suggests that CALM/AF10 exerts its leukemogenic potential through transcriptional deregulation of target genes, including the HOXA gene cluster, therefore interfering with normal hematopoietic differentiation [9, 13–15], through increased genomic instability by reducing global histone H3K79 methylation [16, 17] and through a novel proposed mechanism mediated by the CRM1-dependent nuclear export pathway [18]. The gene discussed is MLLT10; the disease is leukemia.