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


CONCLUSIONS
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.
Fedasenka
U U
UU
Belarusian Research Center for Pediatric Oncology and Hematology, Minsk, Belarus. januarys_v@yahoo.com
Shman
T V
TV
Savitski
V P
VP
Belevcev
M V
MV
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D018365:Neoplasm, Residual / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics* / Q000378:metabolism; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human