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Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I(+), IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia.


Leuk Res. 1999 Apr;23(4):373-84. Unique Identifier : AIDSLINE

To determine activation status of the IL-2R-associated (Jak/STAT) pathway in the HTLV-I infected cells, we examined tyrosine phosphorylation of Jak3, STAT3, and STAT5 in several HTLV-I(+) T-cell lines and in uncultured leukemic T cells isolated from patients with adult T-cell lymphoma/leukemia (ATLL). Constitutive basal phosphorylation of Jak3 and, usually, STAT3 and STAT5 was detected in all four IL-2-independent cell lines tested, but in none of the three IL-2-dependent cell lines. Similarly, there was no detectable basal phosphorylation of Jak3 and STAT5 in the leukemic cells from ATLL patients (0/8 and 0/3, respectively). However, stimulation with IL-2 resulted in Jak3 and STAT5 phosphorylation in both leukemic ATLL cells and IL-2-dependent lines. Furthermore, expression of SHP-1 phosphatase which is a negative regulator of cytokine receptor signaling, was lost in most IL-2 independent cell lines (3/4) but not in the leukemic ATLL cells (0/3). Finally, the HTLV-I(+) T-cell lines (313) but not the control, HTLV-I(-) T-cell lines were resistant to rapamycin and its novel analog RAD. We conclude that (1) HTLV-I infection per se does not result in a constitutive phosphorylation of the Jak3, STAT3, and STAT5 proteins; (2) malignant transformation in at least some cases of ATLL does not require the constitutive, but may require IL-2-induced, activation of the IL-2R Jak/STAT pathway; and (3) there are major differences in T-cell immortalization mechanism(s) which appear to involve SHP-1 and target molecules for rapamycin and RAD.

JOURNAL ARTICLE DNA-Binding Proteins/*METABOLISM Human *HTLV-I HTLV-I Infections/ENZYMOLOGY/*METABOLISM/VIROLOGY Immunosuppressive Agents/PHARMACOLOGY Interleukin-2/*PHYSIOLOGY Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/ENZYMOLOGY/ *METABOLISM/VIROLOGY Lymphocyte Transformation/DRUG EFFECTS/IMMUNOLOGY Phosphorylation Protein-Tyrosine Kinase/*METABOLISM Protein-Tyrosine-Phosphatase/BIOSYNTHESIS/METABOLISM Receptors, Interleukin-2/*METABOLISM Sirolimus/PHARMACOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/IMMUNOLOGY/METABOLISM/VIROLOGY Trans-Activators/*METABOLISM Tumor Cells, Cultured


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