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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



 




Information in this article was accurate in July 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.