Is the mdr 1 gene relevant in chronic lymphocytic leukemia?
Chronic lymphocytic leukemia (CLL) is a progressive disease in which chemotherapy may result in temporary suppression of the peripheral blood lymphocyte count, but cure is not usually possible. Drug resistance mechanisms and the multidrug resistant (MDR) phenotype may be relevant to the therapeutic response. We have studied 34 patients with CLL (seven untreated, 27 treated), screening both DNA and RNA with the mdr 1 gene probe. In pure lymphocyte populations from 10 normal subjects, low levels of mdr 1 RNA expression were found. Eighteen CLL patients (four untreated, 14 treated) had levels of mdr 1 RNA expression above the normal range. No evidence of mdr 1 gene amplification could be found in these patients. Sequential estimations of RNA levels in three patients suggest that malignant lymphocytes in CLL can increase mdr 1 expression in response to chemotherapy and return to basal levels on withdrawal of the treatment. Such data raise important questions about the type of timing of cytotoxic therapy in CLL.
Department of Haematology, University of Wales College of Medicine, Health Park, Cardiff, U.K.
J A
JA
Holmes
A
A
Jacobs
G
G
Carter
J A
JA
Whittaker
D P
DP
Bentley
R A
RA
Padua
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics; D012313:RNA / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012313:RNA