Significance of MDR1, MRP1, GSTp and GSTm mRNA expression in acute lymphoblastic leukemia in

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.

[1]  K. Bhatia,et al.  Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India. , 2000, Leukemia research.

[2]  M. D. Boer,et al.  Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia , 1999, Leukemia.

[3]  J. Philippé,et al.  P‐glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6‐year prospective study , 1999, British journal of haematology.

[4]  D. Venzon,et al.  Acute lymphoblastic leukemia in India: an analysis of prognostic factors using a single treatment regimen. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  O. Legrand,et al.  Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients. , 1998, Blood.

[6]  V. Raina,et al.  Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India , 1998, Annals of Hematology.

[7]  R. Pieters,et al.  Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. , 1998, Blood.

[8]  V. Raina,et al.  Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian patients. , 1998, Leukemia research.

[9]  F. Pinguet,et al.  French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours , 1997, Leukemia.

[10]  M. Slovak,et al.  Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. , 1997, Blood.

[11]  T. Hongo,et al.  In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia. , 1997, Blood.

[12]  K. R. Rajalekshmy,et al.  Prognostic variables and survival in pediatric acute lymphoblastic leukemias: cancer institute experience. , 1996, Pediatric hematology and oncology.

[13]  A. Faussat,et al.  Sequential emergence of MRP‐ and MDR1‐gene over‐expression as well as MDR1‐gene translocation in homoharringtonine‐selected K562 human leukemia cell lines , 1996, International journal of cancer.

[14]  R. Shoemaker,et al.  Overlapping phenotypes of multidrug resistance among panels of human cancer‐cell lines , 1996, International journal of cancer.

[15]  G. Basso,et al.  Prognostic value of rhodamine-efflux and MDR-1/P-170 expression in childhood acute leukemia. , 1995, Leukemia research.

[16]  R. Zittoun,et al.  Expression of multidrug resistance-associated protein (MRP) and multidrug resistance (MDR1) genes in acute myeloid leukemia. , 1995, Leukemia.

[17]  F. Baas,et al.  Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Twentyman MODIFIERS OF MULTIDRUG RESISTANCE , 1995, British journal of haematology.

[19]  B. Nielsen,et al.  Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells. , 1995, Cancer research.

[20]  K. Cowan,et al.  Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia. , 1995, Blood.

[21]  P. Borst,et al.  Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  K. Ganeshaguru,et al.  Expression of the multidrug resistance-associated protein (MRP) in acute leukaemia. , 1994, Leukemia.

[23]  M. Volm,et al.  P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia. , 1994, British Journal of Cancer.

[24]  D. Kufe,et al.  Expression of the multidrug resistance associated protein and P-glycoprotein in doxorubicin-selected human myeloid leukemia cells. , 1994, Blood.

[25]  R. Warnke,et al.  Mdr1 gene expression in childhood acute lymphoblastic leukemias and lymphomas: a critical evaluation by four techniques. , 1994, Leukemia.

[26]  O. Fenneteau,et al.  Expression of the multidrug resistance-associated P-glycoprotein (P-170) in acute lymphoblastic leukemia. , 1993, Blood.

[27]  O. Fardel,et al.  Expression of the multidrug resistance-associated P-glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications. , 1993, Blood.

[28]  S. McKenna,et al.  MULTIDRUG RESISTANCE IN LEUKAEMIA , 1997, Bailliere's clinical haematology.

[29]  A. Duncan,et al.  Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. , 1992, Science.

[30]  S. Bates,et al.  Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell lines. , 1992, Journal of the National Cancer Institute.

[31]  R. Pieters,et al.  Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia. , 1992, British Journal of Cancer.

[32]  W. Ludwig,et al.  Sequential Analysis of P-Glycoprotein Expression in Childhood Acute Lymphoblastic Leukemia , 1992 .

[33]  R. Pieters,et al.  Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia , 1991, The Lancet.

[34]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.