MDR1 and MRP expression in chronic B-cell lymphoproliferative disorders

¹Canberra Clinical School, University of Sydney, The Canberra Hospital, Australia.

|August 29, 1998

Summary

MDR1 and MRP gene expression increases with P-glycoprotein (P-gp) transportable drug exposure in chronic lymphocytic leukaemia (CLL)/non-Hodgkin

Area of Science:

Background:

The role of MDR1 and MRP genes in drug resistance in chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) remains unclear.
Assessing gene expression by combining cell positivity and degree of positivity may reveal relationships with P-glycoprotein (P-gp) transportable drug exposure.

Purpose of the Study:

To investigate the relationship between MDR1 and MRP gene expression levels and exposure to P-gp transportable drugs in CLL/NHL patients.
To determine if MDR1 and MRP gene expression is associated with drug resistance in these patient populations.

Main Methods:

Flow cytometry analysis of MDR1 and MRP expression using specific antibodies in 68 CLL/NHL patients.
Patients were categorized into subgroups based on treatment: untreated, non-P-gp transportable drugs, low-dose P-gp transportable drugs, and high-dose P-gp transportable drugs.

Main Results:

Higher MDR1 expression was observed in patients exposed to high doses of P-gp transportable drugs compared to other groups (P<0.05).
A significant positive correlation was found between MDR1 expression levels and cumulative doses of P-gp transportable drugs (P=0.02).
MRP expression was also higher in the high-dose P-gp transportable drug group (P<0.05), with a trend towards a dose-response correlation (P=0.08).

Conclusions:

MDR1 and MRP gene expression are involved in drug resistance in CLL/NHL patients.
This involvement is specifically linked to treatment with P-glycoprotein (P-gp) transportable drugs.

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