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
| Autor: | Sjozef van Baal, Kelli L. Boyd, Patrick Franken, Gerard Grosveld, Riccardo Fodde, Ugur Ozbek, Ayten Kandilci, Jacqueline Bonten |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pathology medicine.medical_specialty Oncogene Proteins Fusion Chromosomal Proteins Non-Histone Mice Transgenic Biology Translocation Genetic Cell Line Pathology and Forensic Medicine Colony-Forming Units Assay Mice hemic and lymphatic diseases medicine Animals Humans Lymphocytes Acute Undifferentiated Leukemia Progenitor cell Cell Proliferation Acute leukemia Hyperplasia Leukemia Reverse Transcriptase Polymerase Chain Reaction fungi food and beverages Myeloid leukemia Flow Cytometry Hematopoietic Stem Cells medicine.disease Chromosomes Mammalian Immunohistochemistry Survival Analysis Nuclear Pore Complex Proteins Haematopoiesis Ki-67 Antigen Gastric Mucosa Acute Disease Cancer research Female Ectopic expression Stem cell Regular Articles |
| Zdroj: | The American Journal of Pathology. 171:654-666 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2007.060934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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