Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India.
In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTpi, and GSTmu. The expression of beta2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTpi, and in 19 for GSTmu. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTpi, and undetectable to 247% of A549 control cell line for GSTmu mRNA. Increased MRP levels were associated with increased GSTpi and GSTmu levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTpi levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.
Department of Haematology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi.
S
S
Gurbuxani
D
D
Zhou
G
G
Simonin
V
V
Raina
L S
LS
Arya
S
S
Sazawal
J P
JP
Marie
M
M
Bhargava
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007194:India; D007223:Infant; D007527:Isoenzymes / Q000235:genetics; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012737:Sex Factors; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C496556:GSTP1 protein, human