High levels of lung resistance related protein mRNA in leukaemic cells from patients with acute myelogenous leukaemia are associated with inferior response to chemotherapy and prior treatment with mitoxantrone.
Expression of the mdr1 (multidrug resistance), mrp (multidrug resistance associated protein), and lrp (lung resistance related protein) genes is associated with transport related MDR (multidrug resistance). We quantified mRNA levels of these genes using competitive reverse transcription polymerase chain reaction (RT-PCR) in 128 samples of leukaemic cells from 92 patients with acute myelogenous leukaemia (AML). There was a wide variation between the samples in mRNA levels of all three genes. The mean mdr1 mRNA level was 1.3 transcripts per cell (range undetectable to 15.8), the mean mrp level was 7.9 (range 0.1-36.2) and mean lrp 3.9 (range 0.1-29). Lrp mRNA levels were higher in samples drawn at diagnosis from the 15 patients with resistant disease than from the 37 with chemosensitive disease (4.9 SD 3.1 v 2.9 SD 2.3, P = 0.016). Neither mdr1 nor mrp mRNA levels were predictive for response to chemotherapy. In samples from patients who had received chemotherapy, those that had received mitoxantrone (n = 24) had higher lrp mRNA levels (mean 4.8, SD 2.5) than those that had not (n = 20, mean 2.8, SD 2.4, P = 0.012). In conclusion, the results indicate that lrp expression is associated with inferior response to chemotherapy in AML and that lrp expression increases after exposure to mitoxantrone.
Xu
D
D
Department of Medicine, Division of Haematology, Karolinska Hospital, Stockholm, Sweden.
Areström
I
I
Virtala
R
R
Pisa
P
P
Peterson
C
C
Gruber
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
D000970:Antineoplastic Agents; D008942:Mitoxantrone; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein