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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 GSTp expression were significantly higher at relapse than presentation (Pa 0:03 and Pa 0:01, respectively) and remission (Pa 0:007 and Pa 0:003, respectively). MRP1, GSTp and GSTm were expressed simultaneously in several samples with significant association of expression levels (Pa 0:0001). Association with clinicopathological features included higher MDR1 expression with age .15 years (Pa 0:04) and higher MRP1, GSTp, GSTm expression with WBC counts .100 £ 10 9 /l. In 71 patients (age ,25 years), inability to achieve CR was associated with a significantly higher MDR1 mRNA expression (Pa 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. q 2001 Elsevier Science Ireland Ltd. All rights reserved.

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 GSTπ 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, GSTπ and GSTμ 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, GSTπ, GSTμ expression with WBC counts >100×109/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.

In a series of 185 patients (median age 7 years) of acute lymphoblastic leukaemia (ALL) from India, the overall incidence of ALL-1 gene rearrangement using the Southern blot technique was 11.4% (21/185). The incidence amongst the infants (age ≤1 year, 70%) was significantly higher when compared to patients >1–≤10 years (7.4%, P=0.00001) as well as >10 years old (9.3%, P=0.0001). ALL-1 gene rearrangement was associated with significantly higher WBC count (P=0.01) and CD10 negativity (P=0.00000001). Complete remission (CR) and relapse rates in 98 patients evaluable for response to therapy on a uniform therapy protocol was independent of ALL-1 gene status.

In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-β rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2×109/l vs. 103.7×109/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9±10.5, P=0.004). TCR-γ rearrangement in T-ALL was associated with a higher mean WBC count (186.3×109/l vs. 63.4×109/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-β rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45–69%), invariable deletion of Cγ1 and only monoallelic rearrangement for TCR-δ locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.