PMID- 16550188
OWN - NLM
STAT- MEDLINE
DCOM- 20060605
LR  - 20201212
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 12
IP  - 4
DP  - 2006 Apr
TI  - Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human 
      T-lymphotropic virus type I.
PG  - 466-72
AB  - Adult T-cell leukemia-lymphoma (ATLL) is a group of T-cell malignancies caused by 
      infection with human T-lymphotropic virus type I (HTLV-I). Although the 
      pathogenesis of ATLL remains incompletely understood, the viral regulatory 
      protein Tax is centrally involved in cellular transformation. Here we describe 
      the generation of HTLV-I Tax transgenic mice using the Lck proximal promoter to 
      restrict transgene expression to developing thymocytes. After prolonged latency 
      periods, transgenic mice developed diffuse large-cell lymphomas and leukemia with 
      clinical, pathological and immunological features characteristic of acute ATLL. 
      Transgenic mice were functionally immunocompromised and they developed 
      opportunistic infections. Fulminant disease also developed rapidly in SCID mice 
      after engraftment of lymphomatous cells from transgenic mice. Flow cytometry 
      showed that the cells were CD4(-) and CD8(-), but CD44(+), CD25(+) and 
      cytoplasmic CD3(+). This phenotype is indicative of a thymus-derived pre-T-cell 
      phenotype, and disease development was associated with the constitutive 
      activation of NF-kappaB. Our model accurately reproduces human disease and will 
      provide a tool for analysis of the molecular events in transformation and for the 
      development of new therapeutics.
FAU - Hasegawa, Hideki
AU  - Hasegawa H
AD  - Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, 
      Musashimurayama-shi, Tokyo 208-0011, Japan.
FAU - Sawa, Hirofumi
AU  - Sawa H
FAU - Lewis, Martha J
AU  - Lewis MJ
FAU - Orba, Yasuko
AU  - Orba Y
FAU - Sheehy, Noreen
AU  - Sheehy N
FAU - Yamamoto, Yoshie
AU  - Yamamoto Y
FAU - Ichinohe, Takeshi
AU  - Ichinohe T
FAU - Tsunetsugu-Yokota, Yasuko
AU  - Tsunetsugu-Yokota Y
FAU - Katano, Harutaka
AU  - Katano H
FAU - Takahashi, Hidehiro
AU  - Takahashi H
FAU - Matsuda, Junichiro
AU  - Matsuda J
FAU - Sata, Tetsutaro
AU  - Sata T
FAU - Kurata, Takeshi
AU  - Kurata T
FAU - Nagashima, Kazuo
AU  - Nagashima K
FAU - Hall, William W
AU  - Hall WW
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060319
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Biomarkers)
RN  - 0 (CD3 Complex)
SB  - IM
CIN - Nat Med. 2007 May;13(5):527-8. PMID: 17479090
MH  - Animals
MH  - Biomarkers
MH  - CD3 Complex/immunology/metabolism
MH  - Chromosome Mapping
MH  - Chromosomes
MH  - Disease Models, Animal
MH  - Electrophoretic Mobility Shift Assay
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - *Genes, pX
MH  - Human T-lymphotropic virus 1/*genetics/ultrastructure
MH  - Humans
MH  - Immunohistochemistry
MH  - Leukemia, Lymphoid/genetics/immunology/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Neoplasm Transplantation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thymus Neoplasms/immunology/*pathology
MH  - Transgenes
MH  - Transplantation, Homologous
EDAT- 2006/03/22 09:00
MHDA- 2006/06/06 09:00
CRDT- 2006/03/22 09:00
PHST- 2005/08/11 00:00 [received]
PHST- 2005/12/05 00:00 [accepted]
PHST- 2006/03/22 09:00 [pubmed]
PHST- 2006/06/06 09:00 [medline]
PHST- 2006/03/22 09:00 [entrez]
AID - nm1389 [pii]
AID - 10.1038/nm1389 [doi]
PST - ppublish
SO  - Nat Med. 2006 Apr;12(4):466-72. doi: 10.1038/nm1389. Epub 2006 Mar 19.