| Autor: |
Jiang, Xiaoyan, Zhao, Yun, Chan, Wing-Yiu, Vercauteren, Suzanne, Pang, Emily, Kennedy, Sean, Nicolini, Frank, Eaves, Allen, Eaves, Connie |
| Zdroj: |
Blood; May 2004, Vol. 103 Issue: 10 p3897-3904, 8p |
| Abstrakt: |
Ahi-1/AHI-1 (Abelson helper integration site-1) encodes a family of protein isoforms containing one Src homology 3 (SH3) domain and multiple tryptophan-aspartic acid 40 (WD40)–repeat domains. The function of these proteins is unknown, but involvement in leukemogenesis has been suggested by the high frequency of Ahi-1mutations seen in certain virus-induced murine leukemias. Here we show that in both mice and humans, Ahi-1/AHI-1expression is highest in the most primitive hematopoietic cells with specific patterns of down-regulation in different lineages. Cells from patients with chronic myeloid leukemia (CML; n = 28) show elevated AHI-1transcripts in all disease phases and, in chronic phase, in the leukemic cells at all stages of differentiation, including quiescent (G0) CD34+cells as well as terminally differentiating cells. In the most primitive lin–CD34+CD38–CML cells, transcripts for the 2 shorter isoforms of AHI-1are also increased. Although 15 of 16 human lymphoid and myeloid leukemic cell lines showed aberrant control of AHI-1expression, this was not seen in blasts obtained directly from patients with acute Philadelphia chromosome–negative (Ph–) leukemia (n = 15). Taken together, our results suggest that down-regulation of AHI-1expression is an important conserved step in primitive normal hematopoietic cell differentiation and that perturbations in AHI-1expression may contribute to the development of specific types of human leukemia. |
| Databáze: |
Supplemental Index |
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