SET-CAN, the product of the t(9;9) in acute undifferentiated leukemia, causes expansion of early hematopoietic progenitors and hyperproliferation of stomach mucosa in transgenic mice.

Ozbek U, Kandilci A, van Baal S, Bonten J, Boyd K, Franken P, Fodde R, Grosveld GC
Am J Pathol. 2007 171 (2): 654-66

PMID: 17569777 · PMCID: PMC1934515 · DOI:10.2353/ajpath.2007.060934

Leukemia-specific chromosome translocations involving the nucleoporin CAN/NUP214 lead to expression of different fusion genes including DEK-CAN, CAN-ABL, and SET-CAN. DEK-CAN and CAN-ABL1 are associated with acute myeloid leukemia and T-cell acute lymphoblastic leukemia, respectively, whereas SET-CAN was identified in a patient with acute undifferentiated leukemia. In addition, SET is overexpressed in solid tumors of the breast, uterus, stomach, and rectum. Ectopic expression of SET-CAN inhibits vitamin-D(3)-induced differentiation of the human promonocytic U937cells, whereas ectopic SET expression induces differentiation. Here, we assessed the leukemogenic potential of SET-CAN in the hematopoietic system of transgenic mice. Although SET-CAN mice showed expansion of an early progenitor cell pool and partial depletion of lymphocytes, the animals were not leukemia-prone and did not show shortening of disease latency after retroviral tagging. This suggests that SET-CAN expression in acute undifferentiated leukemia might determine the primitive phenotype of the disease, whereas secondary genetic lesions are necessary for disease development. Surprisingly, SET-CAN mice developed spontaneous hyperplasia of the stomach mucosa, which coincided with overexpression of beta-catenin and vastly increased numbers of proliferating gastric mucosa cells, suggesting a role of SET-CAN in proliferation of certain epithelial cells.

MeSH Terms (25)

Acute Disease Animals Cell Line Cell Proliferation Chromosomal Proteins, Non-Histone Chromosomes, Mammalian Colony-Forming Units Assay Female Flow Cytometry Gastric Mucosa Hematopoietic Stem Cells Humans Hyperplasia Immunohistochemistry Ki-67 Antigen Leukemia Lymphocytes Male Mice Mice, Transgenic Nuclear Pore Complex Proteins Oncogene Proteins, Fusion Reverse Transcriptase Polymerase Chain Reaction Survival Analysis Translocation, Genetic

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