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CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34− cells in childhood AML

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Abstract

In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34− subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells were less sensitive to spontaneous apoptosis and had from 1.2- to 5.0-fold higher expression levels of Bcl-2 (eight of ten) and from 1.5- to 28.7-fold higher expression levels of MDR1 (eight of ten). The expression levels of the LRP gene were from 1.1- to 1.8-fold higher in CD34+ subpopulations (five of ten cases), and the expression levels of the BCRP gene were from 1.1- to 22.4-fold higher in CD34+ leukemic cells (six of ten). In all M4 cases, the expression levels of LRP were higher in the CD34− subpopulation. Significant differences in the patterns of genes expression between patients do not allow us to conclude that the CD34+ fractions have more resistant phenotype than the CD34− subpopulations. Nevertheless, distinctions between CD34+ and CD34− cells may lead to different chemosensitivities between leukemic subpopulations in vivo and may determine the alteration of the leukemic immunophenotype during treatment and in relapse.

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Acknowledgements

We would like to thank Utskevich R, Stasevich I, Valochnik A, Savitskaya T, and Krivko M for the data on cytogenetics and FLT3 mutation. This study has been partially supported by a grant (B06-197) from the Belarusian Foundation for Fundamental Research.

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  1. Belarusian Research Center for Pediatric Oncology and Hematology, Minski distr., Pos. Lesnoe, Minsk, Belarus, 223053

    Tatsiana V. Shman, Uladzimir U. Fedasenka, Valery P. Savitski & Olga V. Aleinikova

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  1. Tatsiana V. Shman
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  2. Uladzimir U. Fedasenka
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  3. Valery P. Savitski
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  4. Olga V. Aleinikova
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Correspondence to Tatsiana V. Shman.

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Shman, T.V., Fedasenka, U.U., Savitski, V.P. et al. CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34− cells in childhood AML. Ann Hematol 87, 353–360 (2008). https://doi.org/10.1007/s00277-008-0439-2

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  • DOI: https://doi.org/10.1007/s00277-008-0439-2

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