Significance of MDR1, MRP1, GSTpi and GSTmu mRNA expression in acute lymphoblastic leukemia in Indian patients.
Using, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 167 patients of acute lymphoblastic leukemia (ALL) from India at different stages of the disease (presentation 125, remission 33, first relapse nine), MRP1 and GSTpi expression were significantly higher at relapse than presentation (P=0.03 and P=0.01, respectively) and remission (P=0.007 and P=0.003, respectively). MRP1, GSTpi and GSTmu were expressed simultaneously in several samples with significant association of expression levels (P=0.0001). Association with clinicopathological features included higher MDR1 expression with age >15 years (P=0.04) and higher MRP1, GSTpi, GSTmu expression with WBC counts >100x10(9)/l. In 71 patients (age <25 years), inability to achieve CR was associated with a significantly higher MDR1 mRNA expression (P=0.03) indicating a prognostic significance. However, relapse or shorter Event Free Survival was independent of mRNA expression levels of the four genes. In view of the increased mRNA expression of MRP1/GST at the time of relapse and an association with risk factors such as a high WBC count, further studies directed towards investigating the functional aspects of GSH/GST/MRP1 mediated drug transport are warranted.
Gurbuxani
S
S
Department of Haematology, All India Institute of Medical Sciences, -110029, New Delhi, India.
Singh Arya
L
L
Raina
V
V
Sazawal
S
S
Khattar
A
A
Magrath
I
I
Marie
J
J
Bhargava
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D005260:Female; D015870:Gene Expression; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; 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