Identification of Genes Associated with the Progression of Adult T Cell Leukemia (ATL)

Patients with adult T‐cell leukemia/lymphoma (ATL) exhibit a variety of clinical features, and this disease is therefore clinically subclassified into acute, lymphomatous, chronic, and smoldering types. Acute ATL is a typical leukemic form of ATL with rapid progression, and chronic ATL is a less aggressive clinical form allowing long‐term survival even without chemotherapy. In the present study, we used fresh peripheral blood mononuclear cells (PBMC) from both types of ATL patients to identify molecules that may contribute to the difference between acute and chronic ATL. Isolated mRNAs expressed differentially between the two types of ATL include a T‐cell differentiation antigen (MAL), a lymphoid‐specific member of the G‐protein‐coupled receptor family (EBI‐1/CCR7), a novel human homologue to a subunit (MNLL) of the bovine ubiquinone oxidoreductase complex, and a human fibrinogen‐like protein (hpT49). We found that the former three are upregulated in acute ATL and the last is down‐regulated in both chronic and acute ATL. We speculate that dysregulation of the genes may account for the malignant features of ATL cells, in terms of growth, energy metabolism, and motility.

[1]  M. Marazuela,et al.  Expression of the MAL gene in the thyroid: the MAL proteolipid, a component of glycolipid-enriched membranes, is apically distributed in thyroid follicles. , 1998, Endocrinology.

[2]  W. Blattner,et al.  Adult T‐Cell leukemia/lymphoma: A working point‐score classification for epidemiological studies , 1994, International journal of cancer.

[3]  H. Nomiyama,et al.  Molecular Cloning of a Novel Human CC Chemokine EBI1-ligand Chemokine That Is a Specific Functional Ligand for EBI1, CCR7* , 1997, The Journal of Biological Chemistry.

[4]  M. Yoshida,et al.  Human T-cell leukemia virus type-1 (HTLV-1) Tax is expressed at the same level in infected cells of HTLV-1-associated myelopathy or tropical spastic paraparesis patients as in asymptomatic carriers but at a lower level in adult T-cell leukemia cells. , 1995, Blood.

[5]  M. Kozak Structural features in eukaryotic mRNAs that modulate the initiation of translation. , 1991, The Journal of biological chemistry.

[6]  R. Eddy,et al.  Cloning of human and mouse EBI1, a lymphoid-specific G-protein-coupled receptor encoded on human chromosome 17q12-q21.2. , 1994, Genomics.

[7]  S. Kamihira,et al.  Milk-borne transmission of HTLV-I from carrier mothers to their children. , 1987, Japanese journal of cancer research : Gann.

[8]  E. Kieff,et al.  Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors , 1993, Journal of virology.

[9]  K. Nagata,et al.  Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Tomonaga,et al.  Established IL‐2‐dependent double‐negative (CD4‐ CD8‐) TCRαβ/CD3+ ATL cells: induction of CD4 expression , 1994 .

[11]  E. Wolf,et al.  CCR7 Coordinates the Primary Immune Response by Establishing Functional Microenvironments in Secondary Lymphoid Organs , 1999, Cell.

[12]  Juan P Albar,et al.  Expression of the MAL Gene in the Thyroid: the MAL Proteolipid, a Component of Glycolipid-Enriched Membranes, Is Apically Distributed in Thyroid Follicles. , 1998, Endocrinology.

[13]  T. Gojobori,et al.  Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax , 1991, Molecular and cellular biology.

[14]  S. Tonegawa,et al.  Structure of a cytotoxic T-lymphocyte-specific gene shows a strong homology to fibrinogen beta and gamma chains. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Tomonaga,et al.  Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia. , 1995, Blood.

[16]  T. Sugimura,et al.  Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[17]  H. Towler,et al.  Adult T-cell leukemia : antigen in an ATL cell line and detection of antibodies to the antigen in human sera , 2022 .

[18]  M. A. Alonso,et al.  MAL, a novel integral membrane protein of human T lymphocytes, associates with glycosylphosphatidylinositol‐anchored proteins and Src‐like tyrosine kinases , 1998, European journal of immunology.

[19]  J. Yodoi,et al.  Adult T-cell leukemia: clinical and hematologic features of 16 cases. , 1977, Blood.

[20]  J. Walker,et al.  Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Application of a novel strategy for sequencing proteins using the polymerase chain reaction. , 1992, Journal of molecular biology.

[21]  J. Dooley,et al.  α1-ANTITRYPSIN DEFICIENCY AND LIVER DISEASE , 1982, The Lancet.

[22]  K. Hayashi,et al.  Genetic Alteration of p53 in Some Patients with Adult T‐Cell Leukemia , 1991, Japanese journal of cancer research : Gann.

[23]  R. Burgstahler,et al.  Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2. , 1995, Biochemical and biophysical research communications.

[24]  J. Walker,et al.  Structural analysis of NADH: ubiquinone oxidoreductase from bovine heart mitochondria. , 1995, Methods in enzymology.

[25]  A. Pardee,et al.  Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. , 1993, Nucleic acids research.

[26]  Christine Debouck,et al.  Differential display or differential dismay , 1995 .

[27]  D. Botstein,et al.  The transcriptional program in the response of human fibroblasts to serum. , 1999, Science.

[28]  M. Tomonaga,et al.  Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  M. Deckert,et al.  Endocytosis of GPI-anchored proteins in human lymphocytes: role of glycolipid-based domains, actin cytoskeleton, and protein kinases , 1996, The Journal of cell biology.

[30]  M. Shimoyama,et al.  Diagnostic criteria and classification of clinical subtypes of adult T‐cell leukaemia‐lymphoma , 1991, British journal of haematology.

[31]  T. Fujita,et al.  Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1. , 1992, Journal of immunology.

[32]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[33]  John D. Minna,et al.  Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma , 1980, Proceedings of the National Academy of Sciences.

[34]  First,et al.  Induction of G protein-coupled peptide receptor EBI 1 by human herpesvirus 6 and 7 infection in CD4+ T cells , 1994, Journal of virology.

[35]  Y. Ohno,et al.  Multi‐step Carcinogenesis Model for Adult T‐cell Leukemia , 1989, Japanese journal of cancer research : Gann.

[36]  M Murata,et al.  VIP17/MAL, a proteolipid in apical transport vesicles , 1995, FEBS letters.

[37]  N. Miyamoto,et al.  RISK OF ADULT T-CELL LEUKAEMIA/LYMPHOMA IN HTLV-I CARRIERS , 1987, The Lancet.

[38]  C. Rüegg,et al.  Sequence of a human transcript expressed in T-lymphocytes and encoding a fibrinogen-like protein. , 1995, Gene.

[39]  S. Weissman,et al.  cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[40]  K. Fiedler,et al.  Cloning and characterization of MVP17: A developmentally regulated myelin protein in oligodendrocytes , 1995, Journal of neuroscience research.