Expression of the multidrug resistance gene in myeloid leukemias.
The human multidrug-resistance gene (MDR1) encodes an energy-dependent multidrug efflux protein responsible for the cross-resistance of cultured cells to natural product chemotherapeutic agents such as the anthracyclines and vinca alkaloids. RNA transcript levels were measured in leukemia cells obtained from 15 adult acute nonlymphocytic leukemia (ANLL) cases and 15 cases of chronic myelogenous leukemia (CML). Expression of MDR1 RNA was common in ANLL, and appears to be most frequent in leukemic cells of patients with the poorest response to chemotherapy. Expression of the MDR1 gene was not detectable in the peripheral white blood cells of any of the CML cases during the chronic phase, but was detectable in the immature cells present during this phase of the disease. The cells of the three blastic crisis patients contained detectable levels of MDR1 RNA. These studies support the idea that expression of the MDR1 gene contributes to drug resistance in ANLL, and may play a role in some instances in the drug-resistance of CML in blastic crisis. In contrast, studies of the level of expression of anionic glutathione transferase and DNA polymerase B failed to show any relationship between the RNA transcript levels of these enzymes and responsiveness to chemotherapy.
Sato
H
H
Barrett Center for Cancer Prevention, Research and Treatment, Cincinnati, Ohio 45267-0501.
Gottesman
M M
MM
Goldstein
L J
LJ
Pastan
I
I
Block
A M
AM
Sandberg
A A
AA
Preisler
H D
HD
D000328:Adult; D000368:Aged; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D015152:Blotting, Northern; D004256:DNA Polymerase I / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000032:analysis; D014158:Transcription, Genetic
D012334:RNA, Neoplasm; D005982:Glutathione Transferase; D004256:DNA Polymerase I