Expression of MDR1, LRP, BCRP and BCL-2 genes at diagnosis of childhood ALL: comparison with mrd status after induction therapy

Fedasenka U.U., Shman T.V., Savitski V.P., Belevcev M.V.

to investigate properties of leukemic cells by sorting out children diagnosed with ALL with different response to chemotherapy based on MRD level. Methods: We used a minimal residual disease (MRD) data on day 36 obtained with 3-colour flow cytometry as a reference. In view of MRD results, we used real-time PCR to assess expression levels of multidrug resistance associated genes MDR1, LRP and BCRP, antiapoptotic gene Bcl-2 in initial samples from children diagnosed with ALL. P-gp expression and function in initial samples were analyzed by flow cytometry. Results: Briefly, medians of relative expression levels of MDR1 gene were roughly comparable and in MRD+ group came to 22.8 (0.02–26.6; n = 9) vs 24.8 (3.9–41.4; n = 10) in MRD group. Bcl-2 gene showed tendency to higher expression levels in MRD+ group with median at 5992.9 (521.0–10362.0; n = 9) compared to 3183.6 (1947.9–6581.0; n = 10) in MRD group. LRP gene relative expression levels were similar in both groups and came to 1934.9 (1500.7–3490.4; n = 9) and 1408.5 (665.5–2917.1; n = 10) in MRD+ and MRD groups, respectively. The median of BCRP expression levels in MRD+ group was considerably lower than that in MRD group, namely 76000.0 (48196.2–169230.8; n = 9) and 227967.2 (16683.7–422222.2; n = 10), respectively, but statistical analysis showed no significant difference for this parameter. Conclusion: We investigated expression of multidrug resistance genes MDR1, LRP and BCRP and antiapoptotic gene Bcl-2 in leukemic cells at diagnosis, and MRD level at the end of induction therapy, and could not find obvious relations between these parameters.

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