Quantitative determination of mdr1 gene expression in leukaemic cells from patients with acute leukaemia.
By using a quantitative RNA-RNA solution hybridisation method, the average number of mdr1 RNA transcripts per cell was measured in total nucleic acid extracts of leukaemic cells from patients with acute leukaemia. The results in different types of leukaemia were (number of patients with detectable mdr1 RNA/total number of patients; median number of transcripts per cell in samples with detectable mdr1 RNA); de novo untreated acute myelocytic leukaemia (AML): 20/44; 0.7, secondary acute myelocytic leukaemia: 8/13; 1.1, acute lymphocytic (ALL) and undifferentiated leukaemia: 5/14; 0.6, relapsed leukaemia: 7/15; 0.7. Forty-six patients with de novo untreated acute leukaemia (AML: n = 34, ALL: n = 12) were evaluable for response to induction chemotherapy. Twelve of 18 patients (67%) with detectable mdr1 RNA levels achieved complete remission compared to 23 of 28 (82%) with undetectable levels (P = 0.40). The remission duration tended to be longer among patients with undetectable mdr1 RNA (P = 0.08). Leukaemic cells were analysed on consecutive occasions in 12 patients. The level of expression increased in four and decreased in two. In conclusion, expression of mdr1 RNA is common in acute untreated leukaemia. However, treatment with cytostatic drugs seems only rarely to increase the proportion of leukaemic cells that express mdr1 RNA. Expression of the mdr1 gene could be one of several equally important factors contributing to drug resistance in acute leukaemia.
Gruber
A
A
Division of Medicine, Karolinska Hospital, Stockholm, Sweden.
Vitols
S
S
Norgren
S
S
Areström
I
I
Peterson
C
C
Björkholm
M
M
Reizenstein
P
P
Luthman
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002460:Cell Line; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics*; D008099:Liver / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012008:Recurrence; D012016:Reference Values; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D012334:RNA, Neoplasm; D012313:RNA