C-MAF oncogene dysregulation in multiple myeloma: frequency and biological relevance.
To investigate the frequency and possible biological consequences of c-maf dysregulation, we designed c-maf and IL-4 real-time RT-PCR assays for determination of c-maf and IL-4 mRNA levels. Using the c-maf real-time RT-PCR assay, we tested a panel of 14 B-cell lines, 135 diagnostic bone marrow (BM) samples from patients with multiple myeloma and 10 BM samples from normal donors. In B cell lines and flowsorted CD38++/CD19-/CD56++ myeloma plasma cells (N = 14) the c-maf/GAPDH and IL-4/GAPDH ratios were determined simultaneously using real time RT-PCR. All B cell lines used in the study were characterized by flow cytometry and tested for the presence of Ebstein-Barr virus (EBV). B-cell lines, that were PCR negative for EBV and had a phenotype typical for primary myeloma cells, expressed medium to high levels of c-maf mRNA. However, all EBV PCR positive cell lines, showed a more immature phenotype, lacked expression of aberrant surface markers and contained very low levels of c-maf mRNA. In 4.4% (6/135) of MM patients tested, a c-maf mRNA level comparable to the cell line RPMI 8226 containing at (16:22), translocation was found. In addition, all c-maf positive myeloma cell lines and CD38++/CD19-/CD56++ myeloma plasma cells tested were IL-4 negative. In conclusion, high levels of c-maf mRNA were observed in "true MM cell lines" and 4.4% of MM patients. Further, c-maf dysregulation in myeloma plasma cells did not cause induction of IL-4 transcription.
Rasmussen
Thomas
T
Department of Haematology L 54P4, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. thra@herlevhosp.kbhamt.dk
Knudsen
Lene Meldgaard
LM
Dahl
Inger Marie S
IM
Johnsen
Hans Erik
HE
D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C495607:MAF protein, human; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015847:Interleukin-4