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

Qian Zhang, Benhur Lee, Magda Korecka, Gong Li, Charles Weyland, Steven Eck, Antoine Gessain, Naochimi Arima, Stuart R. Lessin, Leslie M. Shaw, Selina Luger, Malek Kamoun, Mariusz A. Wasik

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31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)373-384
Number of pages12
JournalLeukemia Research
Volume23
Issue number4
DOIs
StatePublished - Apr 1999

Keywords

  • DNA-Binding Proteins/metabolism
  • HTLV-I Infections/enzymology
  • Human T-lymphotropic virus 1
  • Humans
  • Immunosuppressive Agents/pharmacology
  • Interleukin-2/physiology
  • Intracellular Signaling Peptides and Proteins
  • Janus Kinase 3
  • Leukemia-Lymphoma, Adult T-Cell/enzymology
  • Lymphocyte Activation/drug effects
  • Milk Proteins
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases/biosynthesis
  • Protein-Tyrosine Kinases/metabolism
  • Receptors, Interleukin-2/metabolism
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Sirolimus/pharmacology
  • T-Lymphocytes/immunology
  • Trans-Activators/metabolism
  • Tumor Cells, Cultured

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