mRNA expression profile of multidrug resistance genes in childhood acute lymphoblastic leukemia. Low expression levels associated with a higher risk of toxic death.
BACKGROUND
Increased activity of multidrug resistance (MDR) genes has been associated with treatment failure in acute leukemias, although with controversial reports. The objective of the present study was to assess the expression profile of the genes related to MDR: ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP in terms of the clinical and biological variable and the survival of children with acute lymphoblastic leukemia (ALL).


METHODS
The levels of mRNA expression of the drug resistance genes ABCB1, ABCC1, ABCC3, ABCG2, and LRP/MVP were analyzed by quantitative real-time PCR using the median values as cut-off points, in consecutive samples from 140 children with ALL at diagnosis.


RESULTS
Expression levels of the ABCG2 gene in the patient group as a whole (P = 0.05) and of the ABCG2 and ABCC1 genes in patients classified as being at high risk were associated with higher rates of 5-year event-free survival (EFS) (P = 0.04 and P = 0.01). Expression levels of the ABCG2 gene below the median were associated with a greater chance of death related to treatment toxicity for the patient group as a whole (P = 0.009) and expression levels below the median of the ABCG2 and ABCC1 genes were associated with a greater chance of death due to treatment toxicity for the high-risk group (P = 0.02 and P = 0.03, respectively).


CONCLUSIONS
The present data suggest a low participation of the drug efflux genes in treatment failure in patients with childhood ALL. However, the low expression of some of these genes may be associated with a higher death risk related to treatment toxicity.
Cortez
Maria A A
MA
Faculty of Medicine of Ribeirao Preto, Department of Genetics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
Scrideli
Carlos A
CA
Yunes
José A
JA
Valera
Elvis T
ET
Toledo
Sílvia R C
SR
Pavoni-Ferreira
Patrícia C B
PC
Lee
Maria L M
ML
Petrilli
Antônio S
AS
Brandalise
Silvia R
SR
Tone
Luiz G
LG
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D020869:Gene Expression Profiling; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007223:Infant; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D012333:RNA, Messenger / Q000032:analysis; D018570:Risk Assessment; D016019:Survival Analysis; D015996:Survival Rate; D017211:Treatment Failure
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1