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A reappraisal by quantitative flow cytometry analysis of PTEN expression in acute leukemia

Leukemia volume 21, pages 2072–2074 (2007)Cite this article

PTEN is a novel tumor suppressor gene, mapped to 10q23.3, which can dephosphorylate phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P). PtdIns(3,4,5)P mediates growth factor-induced activation of intracellular signaling, in particular through the serine-threonine kinase Akt. Although incidences of inactivation of PTEN in various solid tumors have been described, the role of PTEN in hematological malignancies is unclear. To date, few studies have investigated PTEN expression in primary acute lymphoblastic leukemia (ALL), and the expression of PTEN in acute myeloid leukemia (AML) remains controversial.1, 2 We used quantitative flow cytometry to characterize the expression of PTEN in bone marrow from both healthy donors and acute leukemia patients, and applied the Kolmogorov–Smirnov (KS) statistical test to make analysis more straightforward. Staining intensity was evaluated by comparing binding of anti-PTEN antibody with that of isotype control, and the Kolmogorov–Smirnov test used to calculate a D-value, ranging from 0 to 1, to describe the difference.

We then analyzed the expression of PTEN in AML and ALL blasts. All the leukemia samples included in this study were freshly isolated to avoid the possibility of protein degradation during cycles of freeze–thaw. To identify the blast cells, we stained the leukemic bone marrow samples with CD45 PerCP before fixation. The blast cell population could be distinguished from other cells by the level of CD45 expression and the degree of side scatter. Blasts showed a lower level of CD45 expression than normal cells, and had intermediate side scatter (Figure 1e, g and i). In the 26 patients with de novo AML (1 M0, 2 M1, 11 M2, 3 M3, 6 M4, 2 M5 and 1 M6) included in this study, we observed variable expression levels of PTEN (Figure 1o). Generally, PTEN expression could be detected in all samples tested, although at a level significantly lower than that in normal cell populations (Figure 1f). Interestingly, the two cases of M5 (Figure 1k) showed high levels of PTEN expression with D-values of 0.95 and 0.96 (Figure 1l). Also, in one case of M4, monocyte fraction could be distinguished from blast cells by the level of CD45 expression and side scatter (Figure 1m), and these cells also expressed high levels of PTEN with a D-value of 0.94 (Figure 1n). However, this observation needs to be validated in more patients, and its implications should be further investigated. We could not establish whether PTEN expression level correlated with leukemia FAB subtype because of the limited number of patients in our study.

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References

  1. Grandage VL, Gale RE, Linch DC, Khwaja A . PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways. Leukemia 2005; 19: 586–594.

    Article  CAS  Google Scholar 

  2. Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C et al. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 2006; 20: 911–928.

    Article  CAS  Google Scholar 

  3. Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, Agirre X, Barrios M, Navarro G et al. Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood 2004; 104: 2492–2498.

    Article  CAS  Google Scholar 

  4. Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT et al. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 2006; 441: 518–522.

    Article  CAS  Google Scholar 

  5. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H et al. PTEN dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 2006; 441: 475–482.

    Article  CAS  Google Scholar 

  6. Cheong JW, Eom JI, Maeng HY, Lee ST, Hahn JS, Ko YW et al. Phosphatase and tensin homologue phosphorylation in the C-terminal regulatory domain is frequently observed in acute myeloid leukaemia and associated with poor clinical outcome. Br J Haematol 2003; 122: 454–456.

    Article  CAS  Google Scholar 

  7. Min YH, Cheong JW, Lee MH, Kim JY, Lee ST, Hahn JS et al. Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis. Clin Cancer Res 2004; 10: 5123–5130.

    Article  CAS  Google Scholar 

  8. Zhou M, Gu L, Findley HW, Jiang R, Woods WG . PTEN reverses MDM2-mediated chemotherapy resistance by interacting with p53 in acute lymphoblastic leukemia cells. Cancer Res 2003; 63: 6357–6362.

    CAS  PubMed  Google Scholar 

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Acknowledgements

Dr Shiang Huang was sponsored by the National Outstanding Young Investigator program (no. 30225038).

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  1. Union Hospital of Huazhong University of Science and Technology, Center for Stem Cell Research and application, Wuhan, China

    J Yang, J Liu, J Zheng, W Du, Y He, W Liu & S Huang

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Yang, J., Liu, J., Zheng, J. et al. A reappraisal by quantitative flow cytometry analysis of PTEN expression in acute leukemia. Leukemia 21, 2072–2074 (2007). https://doi.org/10.1038/sj.leu.2404740

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