[cAMP analogue 8-CPT-cAMP inducing differentiation in the M2b subtype of acute myeloid leukemia cell line Kasumi-1].

Abstract

This study was aimed to investigate the possible effects of cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio) adenosine 3', 5'-cyclic monophosphate (8-CPT-cAMP) on the M(2b) subtype of acute myeloid leukemia (AML-M(2b)) cells. AML-M(2b) is characterized by the non-random chromosome translocation t (8; 21) (q22; q22), through which AML1 (acute myeloid leukemia 1) gene on chromosome 21 is fused with ETO (eight twenty-one) gene on chromosome 8, coding correspondent AML1-ETO fusion protein, which plays a crucial role in the leukemogenesis of AML-M(2b). The AML-M(2b) cell line Kasumi-1 cells were used as an in vitro model. The influences of 8-CPT-cAMP on the proliferation and differentiation of Kasumi-1 cells were evaluated according to cellular morphology, changes in cell surface antigen and cell cycle, as well as nitroblue-tetrazolium (NBT) assay. Meanwhile, semi-quantity RT-PCR and Western blot assay were used to detect the degradation of AML1-ETO fusion protein in Kasumi-1 cells before and after the treatment. The results showed that 8-CPT-cAMP (200 micromol/L) could significantly inhibit cell growth and induce differentiation of Kasumi-1 cells. However, it must be pointed out that 8-CPT-cAMP-induced differentiation in Kasumi-1 is not a typical terminal differentiation. Furthermore, 8-CPT-cAMP exerted little influence on the expression of AML1-ETO fusion gene and its product in Kasumi-1 cells. In conclusion, the 8-CPT-cAMP induced differentiation in Kasumi-1 cells. This results may provide experimental and theoretical basis for the breakthrough of differentiation-induced therapy extended to another leukemia.

• Authors: Qi Zhu, Jun-Pei Hu, Pei-Min Jia, Zhen-Yi Wang, Jian-Hua Tong
• Journal: Zhongguo shi yan xue ye xue za zhi (Zhongguo Shi Yan Xue Ye Xue Za Zhi) Vol. 16 Issue 1 Pg. 44-7 (Feb 2008) ISSN: 1009-2137 [Print] China
• PMID: 18315898 (Publication Type: Journal Article)

Chemical References

• AML1-ETO fusion protein, human
• Core Binding Factor Alpha 2 Subunit
• Oncogene Proteins, Fusion
• RUNX1 Translocation Partner 1 Protein
• Thionucleotides
• 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
• Cyclic AMP

Topics

• Cell Transformation, Neoplastic (drug effects)
• Core Binding Factor Alpha 2 Subunit (genetics, metabolism)
• Cyclic AMP (analogs & derivatives, pharmacology)
• Humans
• Leukemia, Myeloid, Acute (genetics, metabolism, pathology)
• Oncogene Proteins, Fusion (genetics, metabolism)
• RUNX1 Translocation Partner 1 Protein
• Thionucleotides (pharmacology)
• Tumor Cells, Cultured