ABR, a novel inducer of transcription factor C/EBPα, contributes to myeloid differentiation and is a favorable prognostic factor in acute myeloid leukemia.

Active related () gene deactivates ras-related C3 botulinum toxin substrate 1 (RAC1), which plays an essential role in regulating normal hematopoiesis and in leukemia. gene, closely related to ABR, acts as a tumor suppressor in chronic myeloid leukemia and has overlapping functions with . Evidence for a putative tumor suppressor role of has been shown in several solid tumors, in which deletion of ABR is present. Our results show downregulation of in AML. A block of ABR prevents myeloid differentiation and leads to repression of the myeloid transcription factor C/EBPα, a major regulator of myeloid differentiation and functionally impaired in leukemia. Conversely, stable overexpression of ABR enhances myeloid differentiation. Inactivation of the known ABR target RAC1 by treatment with the RAC1 inhibitor NSC23766 resulted in an increased expression of C/EBPα in primary AML samples and in AML cell lines U937 and MV4;11. Finally, AML patients with high expression at diagnosis showed a significant longer overall survival and patients who respond to azacitidine therapy showed a significant higher ABR expression. This is the first report showing that expression plays a critical role in both myelopoiesis and AML. Our data indicate the tumor suppressor potential of and underline its potential role in leukemia therapeutic strategies.