Gene expression patterns associated with recurrent chromosomal translocations in acute lymphoblastic leukemia.
We obtained a global view of gene expression in both cell lines and pediatric acute lymphoblastic leukemia (ALL) samples that harbor one of several selected chromosomal abnormalities. When the cell lines were studied alone, we found that these chromosomal abnormalities were associated with the predominant variation in transcriptional programs across the set of cell lines studied. When cell lines and clinical samples were studied together, we found that each chromosomal abnormality (TEL/AML1, BCR/ABL, or MLL abnormalities) was associated with a characteristic gene expression signature that was shared by both cell lines and clinical samples. However, BCR/ABL was associated with a much more heterogeneous pattern of expression than were TEL/AML1 and MLL abnormalities. This observation has important implications for the study of BCR/ABL ALL. In addition, we systematically identified genes whose expression was associated with TEL/AML1, BCR/ABL, or MLL abnormalities in both clinical samples and cell lines. Although some of these genes have previously been described, many have not previously been reported to be associated with one of these chromosomal abnormalities. Notably, we found that the erythropoietin receptor (EPOR) is consistently highly expressed in TEL/AML1 ALL compared with BCR/ABL or MLL.
Fine
Bernard M
BM
Division of Hematology, 269 Campus Dr, CCSR 1155, Stanford University School of Medicine, Stanford, CA 94305-5156, USA. lboxer@stanford.edu
Stanulla
Martin
M
Schrappe
Martin
M
Ho
Minh
M
Viehmann
Susanne
S
Harbott
Jochen
J
Boxer
Linda M
LM
D000293:Adolescent; D001483:Base Sequence; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D016313:Genes, abl; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011519:Proto-Oncogenes; D017467:Receptors, Erythropoietin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; C497422:KMT2A protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein