TCL-1, MTCP-1 and TML-1 gene expression profile in non-leukemic clonal proliferations associated with ataxia-telangiectasia.
We analyzed the role of 4 genes, TCL-1, MTCP-1, TML-1 and ATM, in the early pathogenesis of T cell leukemia, with particular interest in the characteristics of long-standing non-leukemic clonal proliferations in ataxia-telangiectasia (A-T) patients. Five patients were studied: 4 patients had A-T (2 of whom had non-leukemic clonal proliferations [ATCP]), 1 had B cell lymphoma and 1 had T-ALL; a fifth patient with T-PLL did not have A-T. We measured the levels of expression for TCL-1, MTCP-1 and TML-1. TCL-1, not expressed in unstimulated mature T cells, was upregulated in the peripheral blood leukocytes (PBL) of the 2 A-T patients with ATCP. It was also expressed in the malignant cells of the A-T patient with B cell lymphoma and the T-PLL cells of the patient without A-T. In the same cells, MTCP-1 type A was expressed equally in all 5 patients, as well as in the controls; MTCP-1 type B transcripts were not observed. TML-1, also not expressed in unstimulated T cells, was expressed in the PBL of one A-T patient with ATCP and in the leukemic cells of the non-A-T T-PLL patient. These expression patterns were compared to cellular immunophenotypes. The non-leukemic clonal T cell populations had the characteristics of immature T cells. We conclude that TCL-1 and TML-1 play a role in cell proliferation and survival but are not pivotal genes in the progression to malignancy, even when the ATM gene is mutated. Additional genetic alterations must occur to initiate tumorigenesis.
Chun
Helen H
HH
Department of Pathology, School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1732, USA.
Castellví-Bel
Sergi
S
Wang
Zhijun
Z
Nagourney
Robert A
RA
Plaeger
Susan
S
Becker-Catania
Sara G
SG
Naeim
Faramarz
F
Sparkes
Robert S
RS
Gatti
Richard A
RA
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D015463:Leukemia, Prolymphocytic / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics*
C091561:ATM1 protein, S cerevisiae; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C082870:MTCP1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C090851:TCL1A protein, human; C118783:TCL1B protein, human; D014157:Transcription Factors