Expression of MDR1, LRP, BCRP and Bcl-2 genes at diagnosis of childhood all: comparison with MRD status after induction therapy.

AIM: 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.