Identifying progression-associated genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays.
Adult T-cell leukemia/lymphoma (ATL) is associated with human T-lymphotropic virus type-1 (HTLV-1). To understand the changes in expression that occur in the progression of chronic phase of ATL to acute crisis, the gene expression profiles of fresh ATL cells were compared in 4 pairs of samples (progression of chronic to acute phase in 3 patients, as well as 1 typical chronic phase sample vs. 1 typical acute phase sample) using high-density oligonucleotide DNA arrays. We identified 203 genes that were commonly upregulated in acute vs. chronic phase samples including ribosomal proteins, proteosome subunits, eukaryotic translation factors, immunophilins, heat shock proteins and genes important for DNA replication. Additionally, we identified 91 commonly downregulated genes including immune molecules related to MHC and a phosphatase. Several of the genes were previously identified to be associated with the Tax protein of HTLV-1. Some of the upregulated genes were located in amplified regions identified by comparative genomic hybridization in the corresponding chronic/acute ATL sample. Using real-time quantitative PCR, we confirmed the array-results in those specimens analyzed by microarray. These results demonstrated that distinct sets of genes that are known to be critical in cellular transformation and/or activation are up- or down-regulated during the transition to the acute phase of ATL.
Tsukasaki
Kunihiro
K
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, CA, USA. tsukasak@net.nagasaki-u.ac.jp
Tanosaki
Sakae
S
DeVos
Sven
S
Hofmann
Wolf K
WK
Wachsman
William
W
Gombart
Adrian F
AF
Krebs
Johannes
J
Jauch
Anna
A
Bartram
Claus R
CR
Nagai
Kazuhiro
K
Tomonaga
Masao
M
Said
Jonathan W
JW
Koeffler
H Phillip
HP
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D018450:Disease Progression; D020869:Gene Expression Profiling; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D013601:T-Lymphocytes / Q000378:metabolism
D014408:Biomarkers, Tumor