PMID- 9391124
OWN - NLM
STAT- MEDLINE
DCOM- 19980115
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 25
DP  - 1997 Dec 9
TI  - Proliferation of adult T cell leukemia/lymphoma cells is associated with the 
      constitutive activation of JAK/STAT proteins.
PG  - 13897-902
AB  - Human T cell leukemia/lymphotropic virus type I (HTLV-I) induces adult T cell 
      leukemia/lymphoma (ATLL). The mechanism of HTLV-I oncogenesis in T cells remains 
      partly elusive. In vitro, HTLV-I induces ligand-independent transformation of 
      human CD4+ T cells, an event that correlates with acquisition of constitutive 
      phosphorylation of Janus kinases (JAK) and signal transducers and activators of 
      transcription (STAT) proteins. However, it is unclear whether the in vitro model 
      of HTLV-I transformation has relevance to viral leukemogenesis in vivo. Here we 
      tested the status of JAK/STAT phosphorylation and DNA-binding activity of STAT 
      proteins in cell extracts of uncultured leukemic cells from 12 patients with ATLL 
      by either DNA-binding assays, using DNA oligonucleotides specific for STAT-1 and 
      STAT-3, STAT-5 and STAT-6 or, more directly, by immunoprecipitation and 
      immunoblotting with anti-phosphotyrosine antibody for JAK and STAT proteins. 
      Leukemic cells from 8 of 12 patients studied displayed constitutive DNA-binding 
      activity of one or more STAT proteins, and the constitutive activation of the 
      JAK/STAT pathway was found to persist over time in the 2 patients followed 
      longitudinally. Furthermore, an association between JAK3 and STAT-1, STAT-3, and 
      STAT-5 activation and cell-cycle progression was demonstrated by both propidium 
      iodide staining and bromodeoxyuridine incorporation in cells of four patients 
      tested. These results imply that JAK/STAT activation is associated with 
      replication of leukemic cells and that therapeutic approaches aimed at JAK/STAT 
      inhibition may be considered to halt neoplastic growth.
FAU - Takemoto, S
AU  - Takemoto S
AD  - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, 
      Bethesda, MD 20892, USA.
FAU - Mulloy, J C
AU  - Mulloy JC
FAU - Cereseto, A
AU  - Cereseto A
FAU - Migone, T S
AU  - Migone TS
FAU - Patel, B K
AU  - Patel BK
FAU - Matsuoka, M
AU  - Matsuoka M
FAU - Yamaguchi, K
AU  - Yamaguchi K
FAU - Takatsuki, K
AU  - Takatsuki K
FAU - Kamihira, S
AU  - Kamihira S
FAU - White, J D
AU  - White JD
FAU - Leonard, W J
AU  - Leonard WJ
FAU - Waldmann, T
AU  - Waldmann T
FAU - Franchini, G
AU  - Franchini G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Probes)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK3 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Adult
MH  - Base Sequence
MH  - Cell Division
MH  - DNA Probes/genetics
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Human T-lymphotropic virus 1/pathogenicity
MH  - Humans
MH  - Janus Kinase 3
MH  - Leukemia-Lymphoma, Adult T-Cell/genetics/*metabolism/*pathology
MH  - *Milk Proteins
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - STAT1 Transcription Factor
MH  - STAT3 Transcription Factor
MH  - STAT5 Transcription Factor
MH  - Time Factors
MH  - Trans-Activators/*metabolism
PMC - PMC28404
EDAT- 1998/02/12 00:00
MHDA- 1998/02/12 00:01
PMCR- 1998/06/09
CRDT- 1998/02/12 00:00
PHST- 1998/02/12 00:00 [pubmed]
PHST- 1998/02/12 00:01 [medline]
PHST- 1998/02/12 00:00 [entrez]
PHST- 1998/06/09 00:00 [pmc-release]
AID - 3231 [pii]
AID - 10.1073/pnas.94.25.13897 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13897-902. doi: 
      10.1073/pnas.94.25.13897.