Abstract
Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.
Highlights
The results of chemotherapy on childhood acute lymphoblastic leukaemia (ALL) have been markedly improved during the past decade (Riehm et al, 1992)
The aim of the present investigation was to assess the prognostic value of P-glycoprotein and glutathione S-transferase x in a retrospective study of 104 children with untreated non-B-acute lymphoblastic leukaemia using a immunohistochemical method
For measuring P-glycoprotein (P-170) and glutathione Stransferase i (GST-r) cell samples were resuspended in Hanks' balanced salt solution (Biochrom, Berlin, Germany) and the viability of cells was tested by staining with methylene blue
Summary
Blast cells from bone marrow or peripheral blood from 111 children (52 boys and 59 girls) with newly diagnosed non-Btype acute lymphoblastic leukaemia (ALL) were collected and cryopreserved. Complete remission was diagnosed if the blast cell content was less than 5% in an otherwise normocellular marrow on day 33 after the onset of the therapy without evidence of blast cells at extramedullary sites. Patients were diagnosed to have isolated bone marrow relapses if they had > 25% blast cells in the marrow with no evidence of leukaemia at extramedullary sites. Marrow involvement was diagnosed in patients with proven leukaemia at extramedullary sites and at least 5% detectable bone marrow blasts. [ALL-VII/81, ALL-VIII/87 (Zintl et al, 1993) and ALL-BFM-90 (Riehm et al, 1992)] These treatment protocols consist of induction therapy with prednisone, vincristine, daunorubicin and L-asparaginase followed by consolidation therapy with cyclophosphamide, cytarabine, 6-mercaptopurine and intrathecal methotrexate (MTX). All cell samples contained at least 80% blast cells, examined by May-GriiwaldGiemsa staining
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