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A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemia

Leukemia volume 21, pages 1093–1097 (2007)Cite this article

A Retraction to this article was published on 11 August 2010

Acute myeloid leukemia (AML) is a clonal hematopoietic disorder that develops as a result of cumulative genetic and epigenetic events that affect key regulatory genes conferring a proliferative growth and survival advantage. Both intrinsic and acquired chemotherapeutic resistance remain as major limitations in the successful treatment of AML.1 Evidence suggest that drug resistance mechanisms other than multidrug resistance phenotype are involved, such as reduced intracellular concentrations of ara-CTP, the active triphosphorylated form of Ara-C.1 However, Ara-C resistance-related changes in AML cells have not been well investigated using a genome-wide approach. Murine leukemia cell lines provide a readily available and more uniform disease platform for analysis of gene expression. Comparison of gene expression patterns between Ara-C-sensitive and -resistant cell lines should provide a valuable insight into the development of chemotherapy resistance.

We have generated Ara-C-resistant murine leukemia cell lines, B117H and B140H, from their Ara-C-sensitive parental cell lines, B117P and B140P, respectively.2, 3 To characterize the sensitive and resistant lines, their chromosomal features were examined using spectral karyotyping analysis as described previously.4 It is known that cell lines tend to manifest chromosomal abnormalities, especially after an extensive passaging process. As expected, both Ara-C-sensitive and -resistant cells show multiple chromosomal alterations, including chromosome loss, translocation and amplification (data not shown). Consistent with our previous observation on proviral integration patterns, the resistant cells represent a cytogenetic feature related to parental cells. In addition, new chromosomal changes were also found in resistant cells (data not shown), suggesting that multiple clonal, extensive chromosomal aberrations occur after exposure to increasing doses of Ara-C.

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Acknowledgements

We acknowledge support from the Leukemia and Lymphoma Society of America (LLS 7019-04, Specialized Center of Research).

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Author notes

  1. B Yin and M L Tsai: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Genetics, Cell Biology and Development, The Cancer Center at the University of Minnesota, University of Minnesota, Minneapolis, MN, USA

    B Yin, M L Tsai, D E Hasz, S K Rathe & D A Largaespada

  2. Section of Hematology/Oncology, and the Cancer Research Center, The University of Chicago, Chicago, IL, USA

    M M Le Beau

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  1. B Yin
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  2. M L Tsai
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  3. D E Hasz
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  4. S K Rathe
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  5. M M Le Beau
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  6. D A Largaespada
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Correspondence to D A Largaespada.

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Yin, B., Tsai, M., Hasz, D. et al. A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemia. Leukemia 21, 1093–1097 (2007). https://doi.org/10.1038/sj.leu.2404595

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