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题目:: Stromal cell protection of B-lineage acute lymphoblastic leukemic cells during chemotherapy requires active Akt.
作者:: Wang(Lin),Fortney(James E),Gibson(Laura F)
状态:: 发布时间2004-05-25 , 更新时间 2016-10-25
期刊:: Leuk Res
摘要:: Several studies document ALL cell response to survival signals from bone marrow stromal cells. The current study suggests a requirement for active Akt in ALL cells for optimal stromal cell protection during chemotherapy. ALL cells expressing dominant negative Akt were not efficiently rescued from Ara-C or etoposide-induced apoptosis by stromal cell co-culture. In addition, inhibition of ALL cell PI-3 kinase activity diminished stromal cells support of tumor cells during treatment. ALL cell lines co-cultured with bone marrow stromal cells during chemotherapy maintained higher levels of phosphorylated Akt protein and reduced PP2A activity when compared to ALL cells treated in medium alone. Chemotherapy-induced PARP and Bcl-2 cleavage was reduced in ALL cells cultured with a stromal cell layer compared to tumor cells exposed to drug in medium alone. However, interaction with stromal cells was not able to efficiently block treatment-induced PARP or Bcl-2 cleavage in leukemic cells with blunted Akt activity. These data suggest a pivotal role for Akt in mediating stromal cell regulation of ALL cell apoptosis.
语言:: eng
DOI:

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