Jurnal Internasional Insufisiensi Bcor meningkatkan inisiasi dan perkembangan sindrom myelodysplastic
BCOR BCL-6 corepressor (BCOR) coding, is X-linked and targeted by somatic mutations in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice that lacked Bcor exon 4 (19459] Bcor E4 / y in the hematopoietic compartment developed TCH-lymphoblastic acute leukemia (T-ALL). Here, we analyze mice that lack Bcor exon 9 and 10 (1945977) Bcor E9-10 / y which express carboxyl-truncated BCOR that fails to interact with the core effector component complex repressive policomb 1.1. Bcor E9-10 / y mice developed lethal T-ALL in a manner similar to Bcor E4 / y mice, whereas Bcor E9 -10 / y hematopoietic cells showed a growth advantage in the myeloid compartment which was further enhanced by the simultaneous removal of Tet2 . Tet2 /  Bcor E9-10 / y mice developed lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis, and morphological dysplasia of blood cells. Tet2 / Bcor E9-10 / y MDS cells reproduce MDS or evolve into MDS / myeloproliferative neoplasms which are lethal to secondary recipients. The transcription profile reveals the depression of the myeloid regulator gene from the family Cebp and the Hoxa cluster gene at Bcor E9-10 / y progenitor cells and activation of the p53 target gene specifically on MDS erythroblasts where massive apoptosis occurs. Our results revealed BCOR tumor suppressor function in myeloid malignancy and highlighted the effects of Bcor deficiencies in MDS initiation and development.