Human chronic lymphocytic leukemia cells regularly express mRNAs of the protooncogenes lck and c-fgr.

Protooncogenes, the cellular homologues of transforming retroviral oncogenes, have been suggested to participate in malignant transformation of various cell types. The role activated protooncogenes might play in chronic lymphocytic leukemia (CLL) is not yet clear. We investigated the expression of the protooncogenes lck and c-fgr encoding two protein tyrosine kinases by Northern-blot analysis in 21 patients with B-CLL and transcripts of both genes were detected in all cases. In contrast to CLL B cells, normal B cells from peripheral blood of a healthy donor separated by magnetic sorting did not express c-fgr and lck. The results suggest a possible role for these two protooncogenes of the src family in the activation and/or transformation of human B lymphocytes.

[1]  E. Cronkite,et al.  Clinical staging of chronic lymphocytic leukemia. , 1975, Blood.

[2]  R. Benarous,et al.  Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons. , 1989, Gene.

[3]  Michael A. Bookman,et al.  The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56 lck , 1988, Cell.

[4]  H. Varmus.  The molecular genetics of cellular oncogenes. , 1984, Annual review of genetics.

[5]  Normal cellular counterparts of B cell chronic lymphocytic leukemia. , 1987 .

[6]  C. Milstein,et al.  Human immunoglobulin heavy chain genes: evolutionary comparisons of C mu, C delta and C gamma genes and associated switch sequences. , 1981, Nucleic acids research.

[7]  A. Freedman,et al.  The relationship of chronic lymphocytic leukemia to normal activated B cells. , 1990, Leukemia & lymphoma.

[8]  S. Ferrari,et al.  Expression of human c‐fes one‐gene occurs at detectable levels in myeloid but not in lymphoid cell populations , 1985, British journal of haematology.

[9]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[10]  J. Clauvel,et al.  Surface IgD in Immunoproliferative Disorders , 1974, Scandinavian journal of immunology.

[11]  K. Shimotohno,et al.  Ick Suppresses Gene Expression from Various Promoters Including Human T‐Cell Leukemia Virus Type I Promoter , 1990, Japanese journal of cancer research : Gann.

[12]  Andreas Radbruch,et al.  High gradient magnetic cell separation with MACS. , 1990, Cytometry.

[13]  D T Denhardt,et al.  A membrane-filter technique for the detection of complementary DNA. , 1966, Biochemical and biophysical research communications.

[14]  C. Disteche,et al.  Localization of a lymphocyte-specific protein tyrosine kinase gene (lck) at a site of frequent chromosomal abnormalities in human lymphomas. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Bloch,et al.  Immunoglobulins on the surface of neoplastic lymphocytes. , 1972, The New England journal of medicine.

[16]  N. Kay,et al.  Malignant chronic lymphocytic leukemia B cells express interleukin 2 receptors but fail to respond to interleukin 2's proliferative signal. , 1987, Leukemia.

[17]  S. Leevers,et al.  Regulation of C‐FGR proto‐oncogene expression in epstein‐barr virus infected B‐cell lines , 1990, International journal of cancer.

[18]  T. Ley,et al.  fgr proto-oncogene mRNA induced in B lymphocytes by Epstein–Barr virus infection , 1986, Nature.

[19]  V. Diehl,et al.  Heterogeneous expression of proto‐oncogenes in Hodgkin's disease derived cell lines , 1990, Hematological oncology.

[20]  J. Preud’homme,et al.  Surface bound immunoglobulins as a cell marker in human lymphoproliferative diseases. , 1972, Blood.

[21]  C. Rudd,et al.  The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[22]  T. Yamamoto,et al.  Specific expression of human c-fgr in natural immunity effector cells , 1990, Molecular and cellular biology.

[23]  E. Krebs,et al.  A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA , 1985, Cell.

[24]  K. C. Reed,et al.  Rapid transfer of DNA from agarose gels to nylon membranes. , 1985, Nucleic acids research.

[25]  E. Krebs,et al.  Regulation of pp56lck during T‐cell activation: functional implications for the src‐like protein tyrosine kinases. , 1987, The EMBO journal.

[26]  R. Beelen,et al.  Isolation of human splenic macrophages and lymphocytes by countercurrent centrifugal elutriation. , 1984, Journal of immunological methods.

[27]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[28]  T. Ley,et al.  Tissue-specific expression and developmental regulation of the human fgr proto-oncogene , 1989, Molecular and cellular biology.

[29]  J. Gabrilove,et al.  Specific expression of the human cellular fps/fes-encoded protein NCP92 in normal and leukemic myeloid cells. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[30]  E. Sausville,et al.  Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. , 1987, Oncogene research.

[31]  C. Rudd,et al.  The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Bishop.  The molecular genetics of cancer. , 1987, Science.

[33]  A. V. D. van den Ouweland,et al.  The structure of the human c‐fes/fps proto‐oncogene. , 1985, The EMBO journal.

[34]  H Tesch,et al.  CD20 positive human B lymphocytes separated with the magnetic cell sorter (MACS) can be induced to proliferation and antibody secretion in vitro. , 1989, Journal of immunological methods.

[35]  R. Perlmutter,et al.  Structure and expression of Ick transcripts in human lymphoid cells , 1988 .

[36]  K. Semba,et al.  Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. , 1987, Oncogene.

[37]  B. White,et al.  Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. , 1982, The Journal of biological chemistry.

[38]  E. Kieff,et al.  Long internal direct repeat in Epstein-Barr virus DNA , 1982, Journal of virology.

[39]  G. Mardon,et al.  Isolation of duplicated human c-src genes located on chromosomes 1 and 20 , 1985, Molecular and cellular biology.

[40]  D. Gallwitz,et al.  Structure of two human beta‐actin‐related processed genes one of which is located next to a simple repetitive sequence. , 1983, The EMBO journal.