High expression of the mdr3 multidrug-resistance gene in advanced-stage
chronic lymphocytic leukemia
P Sonneveld, K Nooter, JT Burghouts, H Herweijer, HJ Adriaansen and JJ van Dongen
Department of Hematology, Erasmus University, Rotterdam, The Netherlands.
Chronic lymphocytic leukemia (CLL) is characterized by an often indolent
course with a poor therapeutic response at advanced stage. We investigated
the expression of the human multidrug resistance genes mdr1 and mdr3 in 31
patients with CLL. Using specific probes for mdr1 and mdr3 mRNA,
respectively, expression of both genes could be found in 29 of 31 patients.
Of those, nine had high expression of mdr1 and 13 of mdr3. Although 29 of
31 patients showed coexpression of mdr1 and mdr3, the mRNA levels were not
interrelated. Prior treatment did not significantly influence the level of
mdr1 or mdr3 expression. In patients with advanced CLL (Rai stage 3 + 4)
the mdr3 expression was significantly higher than in early-stage CLL (Rai
stage 0 to 2) (mean +/- SEM, 25.4 +/- 4.2 U v 4.2 +/- 1.1 U; P less than
.0001). Such a difference was not present for mdr1 expression (21.5 +/- 4.3
U v 10.7 +/- 3.1 U; P = .09). These data indicate that advanced-stage CLL
is associated with an increased mdr3 expression, which may concur with a
decreased sensitivity to chemotherapy.
Volume 79,
Issue 6,
pp. 1496-1500,
03/15/1992
Copyright © 1992 by The American Society of Hematology
