title: Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation.
abstract: Multidrug resistance gene (mdrl) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20-25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. the cell fraction with low DNR content had higher (3.8-40 times)mdr1 mRNA levels in 10/10 patients and higher (1.4-26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation. In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.
authors.affiliation: Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: E
authors.initials: E
authors.lastname: Knaust
authors.forename: P
authors.initials: P
authors.lastname: Pisa
authors.forename: K
authors.initials: K
authors.lastname: Palucka
authors.forename: J
authors.initials: J
authors.lastname: Lundeberg
authors.forename: I
authors.initials: I
authors.lastname: Areström
authors.forename: C
authors.initials: C
authors.lastname: Peterson
authors.forename: A
authors.initials: A
authors.lastname: Gruber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003630:Daunorubicin / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D003630:Daunorubicin