PU.1 silencing leads to terminal differentiation of erythroleukemia cells.
The transcription factor PU.1 plays a central role in development and differentiation of hematopoietic cells. Evidence from PU.1 knockout mice indicates a pivotal role for PU.1 in myeloid lineage and B-lymphocyte development. In addition, PU.1 is a key player in the development of Friend erythroleukemia disease, which is characterized by proliferation and differentiation arrest of proerythrocytes. To study the role of PU.1 in erythroleukemia, we have used murine erythroleukemia cells, isolated from Friend virus-infected mice. Expression of PU.1 small interfering RNA in these cells led to significant inhibition of PU.1 levels. This was accompanied by inhibition of proliferation and restoration in the ability of the proerythroblastic cells to produce hemoglobin, i.e., reversion of the leukemic phenotype. The data suggest that overexpression of PU.1 gene is the immediate cause for maintaining the leukemic phenotype of the disease by retaining the self-renewal capacity of transformed erythroblastic cells and by blocking the terminal differentiation program towards erythrocytes.
Atar
Orna
O
The Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Levi
Ben-Zion
BZ
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006454:Hemoglobins / Q000096:biosynthesis / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
D006454:Hemoglobins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1