Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia.
Interferon regulatory factors IRF-1 and IRF-2, the two mutually antagonistic factors, fluctuate during the cell cycle and play an important role in normal and neoplastic growth processes. The relative levels of these two transcripts were analyzed in 5 normal and 43 acute myeloid leukemia (AML) bone marrow (BM) specimens by a semiquantitative RT-PCR method. IRF-1 and IRF-2 cDNA sequences were coamplified using primers that were designed to span regions of high homology between the genes. Each primer can anneal equally to both IRF-1 and IRF-2 sequences. Hence, the relative amount of amplified products from each cDNA species provides an estimation of proportional concentration of the RNA transcripts in the test sample. Results indicate expression of both the transcripts on all the leukemia and lymphoma cell lines tested, normal and AML BM. Significantly higher IRF-1:IRF-2 ratio was observed in normal as compared to AML BM (p = 0.007). There was no correlation with clinical factors such as FAB subtype. A single dose of amifostine or three daily doses of recombinant IL-4 were administered to 5 and 8 AML patients, respectively. The changes in the expression of these transcripts were studied prior to administration of the agent (d0) and after 3 days (d3). IL-4 treatment showed significant increase in the IRF-1:IRF-2 ratio in 4 of 8 patients (p = 0.05); amifostine treatment did not show any appreciable change.
Perambakam
S
S
Rush Cancer Institute, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
Li
B
B
Preisler
H
H
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000494:pharmacology / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D015847:Interleukin-4 / Q000494:pharmacology / Q000627:therapeutic use; D020014:K562 Cells / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis* / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism; D020298:U937 Cells / Q000378:metabolism
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D004999:Amifostine