Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides: implications for the involvement of WT1 in leukemogenesis
- PMID: 8639907
Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides: implications for the involvement of WT1 in leukemogenesis
Abstract
We have previously reported expression of WT1 in acute leukemia. To elucidate its biological significance, we examined the effect of the suppression of the WT1 expression by WT1 antisense oligomers on the growth of the leukemic cells expressing WT1. When 20 different WT1 antisense (AS) oligomers covering from the 5' cap sites of the WT1 gene to the 3' end were examined for the inhibitory effect on the growth of K562 cells expressing WT1, four WT1 AS oligomers inhibited the cell growth, whereas WT1 sense and random sequence oligomers had no effect on the cell growth of K562. Moreover, WT1 AS oligomers significantly inhibited the growth of the clonogenic cells of fresh leukemic cells in six of 14 patients with acute myeloid leukemia, in one of two patients with chronic myelogenous leukemia (CML) chronic phase, and in one of one patient with CML blastic crisis. However, these oligomers did not inhibit normal colony-forming unit-granulocyte-macrophage. Western blot analysis clearly demonstrated the significant reduction in the WT1 protein levels in the K562 and fresh leukemic cells that were treated with the WT1 AS oligomers, confirming that the inhibitory effect of the WT1 AS oligomers on the cell growth operates via the reduction in the WT1 protein levels. These results show that WT1 plays an important role in leukemogenesis.
Similar articles
-
A WT1 antisense oligonucleotide inhibits proliferation and induces apoptosis in myeloid leukaemia cell lines.Oncogene. 1996 Mar 7;12(5):1005-14. Oncogene. 1996. PMID: 8649791
-
Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias.Leukemia. 1995 Jun;9(6):1060-7. Leukemia. 1995. PMID: 7596170
-
[Effect of WT1 antisense oligonucleotide on proliferation and apoptosis of human leukemia cells].Zhonghua Xue Ye Xue Za Zhi. 1999 Dec;20(12):631-3. Zhonghua Xue Ye Xue Za Zhi. 1999. PMID: 11721364 Chinese.
-
Wilms tumor gene (WT1) as a new marker for the detection of minimal residual disease in leukemia.Leuk Lymphoma. 1998 Jun;30(1-2):55-61. doi: 10.3109/10428199809050929. Leuk Lymphoma. 1998. PMID: 9669676 Review.
-
[Expression of WT1 gene in leukemia and its significance].Zhonghua Xue Ye Xue Za Zhi. 1998 Jan;19(1):46-8. Zhonghua Xue Ye Xue Za Zhi. 1998. PMID: 10921100 Review. Chinese. No abstract available.
Cited by
-
Wilms' tumor gene WT1: its oncogenic function and clinical application.Int J Hematol. 2001 Feb;73(2):177-87. doi: 10.1007/BF02981935. Int J Hematol. 2001. PMID: 11372729 Review.
-
The possible role and application of WT1 in human leukemia.Int J Hematol. 2001 Jan;73(1):39-46. doi: 10.1007/BF02981901. Int J Hematol. 2001. PMID: 11372753 Review.
-
Wilms tumor gene peptide-based immunotherapy for patients with overt leukemia from myelodysplastic syndrome (MDS) or MDS with myelofibrosis.Int J Hematol. 2003 Jul;78(1):56-61. doi: 10.1007/BF02983241. Int J Hematol. 2003. PMID: 12894852 Clinical Trial.
-
WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.Cancer Immunol Immunother. 2004 Jul;53(7):617-24. doi: 10.1007/s00262-003-0498-0. Epub 2004 Feb 7. Cancer Immunol Immunother. 2004. PMID: 15175906 Free PMC article.
-
Understanding WT1 Alterations and Expression Profiles in Hematological Malignancies.Cancers (Basel). 2023 Jul 4;15(13):3491. doi: 10.3390/cancers15133491. Cancers (Basel). 2023. PMID: 37444601 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous
