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Acute Leukemias

AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2

Leukemia volume 23, pages 1598–1604 (2009)Cite this article

Abstract

AML1-ETO fusion gene is generated from chromosomal translocation t(8;21) mainly in acute myeloid leukemia M2 subtype (AML-M2). Its spliced variant transcript, AML1-ETO9a, rapidly induces leukemia in murine model. To evaluate its clinical significance, AML1-ETO9a expression was assessed in 118 patients with t(8;21) AML-M2, using qualitative and nested quantitative reverse transcriptase (RT)–PCR methods. These cases were accordingly divided into the AML1-ETO9a-H group (n=86, positive for qualitative RT–PCR, with higher level of AML1-ETO9a by quantitative RT–PCR) and the AML1-ETO9a-L group (n=32, negative for qualitative RT–PCR, with lower but still detectable level of AML1-ETO9a by quantitative RT–PCR). C-KIT expression was significantly increased in the AML1-ETO9a-H group, as compared with the AML1-ETO9a-L group. Of the 36 patients harboring C-KIT mutations, 32 patients overexpressed AML1-ETO9a (P=0.0209). Clinically, AML1-ETO9a-H patients exhibited significantly elevated white blood cells count, less bone marrow aberrant myelocytes, increased CD56 but decreased CD19 expression (P=0.0451, P=0.0479, P=0.0149 and P=0.0298, respectively). Moreover, AML1-ETO9a overexpression was related to short event-free and overall survival time (P=0.0072 and P=0.0076, respectively). Taken together, these data suggest that AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) AML-M2.

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Acknowledgements

The authors thank Dr Dong Er Zhang from University of California San Diego for the critical review of the article. This work was supported, in part, by the Chinese National Key Program for Basic Research (973:2004CB518606), the Chinese National High Tech Program (863:2006AA02A301 and 863:2006AA02A405), the National Natural Science Foundation of China (30772480, 30623010 and 30521003), the Key Discipline Program of Shanghai Municipal Education Commission (Y0201) and the Shanghai Commission of Science and Technology (04DZ14004, 064119666, 06DZ22021).

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  1. B Jiao and C-F Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    B Jiao, C-F Wu, Y Liang, H-M Chen, S-M Xiong, B Chen, J-Y Shi, Y-Y Wang, J-H Wang, Y Chen, J-M Li, Z-X Shen, B-W Gu, W-L Zhao, Z Chen & S-J Chen

  2. Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    L-J Gu & J-Y Tang

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Correspondence to W-L Zhao or S-J Chen.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Jiao, B., Wu, CF., Liang, Y. et al. AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2. Leukemia 23, 1598–1604 (2009). https://doi.org/10.1038/leu.2009.104

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