Differential expression of TCL1 during pre-B-cell acute lymphoblastic leukemia progression.
Nonrandom, recurring chromosomal translocations are critical events in the pathogenesis of leukemia. The recently identified TEL/AML1 (CBFA2/EVT6) fusion gene occurs as a result of the t(12;21)(p13;q22) in approximately 25% of children with diagnosed pre-B-cell acute lymphoblastic leukemia (PBC-ALL). To identify changes in gene expression patterns that occur during PBC-ALL disease progression, we used cDNA microarrays to compare expressed sequences from the AT-1 and AT-2 cell lines. These cell lines, from the same patient, were established from two distinct stages of PBC-ALL disease progression, namely, first and second relapse. Analysis of both cell lines with spectral karyotying (SKY) revealed an insertion of chromosome 8 into chromosome 5 and a previously undetected translocation in AT-2 involving chromosomes 1 and 17. Hybridization of cDNA microarrays identified the TCL1 transcript as being overexpressed in the AT-2 cell line relative to AT-1. Northern blot analysis showed an eightfold increase of the TCL1 transcript in AT-2 over AT-1 cells. Western blot analysis showed that the TCL1 protein was expressed more than 50-fold higher in AT-2 than AT-1 cells. TCL1 expression was correlated with TEL expression by reintroducing TEL into AT-2 cells and demonstrating that those cells expressing TEL at high levels showed a decreased expression of endogenous TCL1.
Fears
S
S
Section of Hematology, Oncology Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Chakrabarti
S R
SR
Nucifora
G
G
Rowley
J D
JD
D000208:Acute Disease; D002454:Cell Differentiation; D002675:Child, Preschool; D020223:Chromosome Painting; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000648:ultrastructure; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000648:ultrastructure; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000648:ultrastructure; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C090851:TCL1A protein, human; C102421:TEL-AML1 fusion protein