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

被引:28
作者
Zhang, QA
Lee, B
Korecka, M
Li, G
Weyland, C
Eck, S
Gessain, A
Arima, N
Lessin, SR
Shaw, LM
Luger, S
Kamoun, M
Wasik, MA
机构
[1] Univ Penn Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Univ Penn Ctr, Dept Hematol Oncol, Philadelphia, PA 19104 USA
[3] Univ Penn Ctr, Dept Dermatol, Philadelphia, PA 19104 USA
[4] Inst Pasteur, Paris, France
[5] Kagoshima Univ, Kagoshima 890, Japan
基金
美国国家卫生研究院;
关键词
IL-2R signaling; malignant T cells; JAK5; kinase; STAT; 5; protein; SHP-1; phosphatase;
D O I
10.1016/S0145-2126(98)00173-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 Tines (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. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:373 / 384
页数:12
相关论文
共 72 条
[61]  
TOKUDOME S, 1989, CANCER RES, V49, P226
[62]  
WASIK MA, 1990, J IMMUNOL, V144, P3334
[63]   Analysis of IL-2, IL-4 and their receptors in clonally-related cell lines derived from a patient with a progressive cutaneous T-cell lymphoproliferative disorder [J].
Wasik, MA ;
Seldin, DC ;
Butmarc, JR ;
Gertz, R ;
Marti, R ;
Maslinski, W ;
Kadin, ME .
LEUKEMIA & LYMPHOMA, 1996, 23 (1-2) :125-&
[64]   Increased serum concentration of the soluble interleukin-2 receptor in cutaneous T-cell lymphoma - Clinical and prognostic implications [J].
Wasik, MA ;
Vonderheid, EC ;
Bigler, RD ;
Marti, R ;
Lessin, SR ;
Polansky, M ;
Kadin, ME .
ARCHIVES OF DERMATOLOGY, 1996, 132 (01) :42-47
[65]   Suppression of proliferation and phosphorylation of Jak3 and STAT5 in malignant T-cell lymphoma cells by derivatives of octylamino-undecyl-dimethylxanthine [J].
Wasik, MA ;
Nowak, I ;
Zhang, Q ;
Shaw, LM .
LEUKEMIA & LYMPHOMA, 1998, 28 (5-6) :551-560
[66]   INVOLVEMENT OF THE JAK-3 JANUS KINASE IN SIGNALING BY INTERLEUKIN-2 AND INTERLEUKIN-4 IN LYMPHOID AND MYELOID CELLS [J].
WITTHUHN, BA ;
SILVENNOINEN, O ;
MIURA, O ;
LAI, KS ;
CWIK, C ;
LIU, ET ;
IHLE, JN .
NATURE, 1994, 370 (6485) :153-157
[67]   CONSTITUTIVE ACTIVATION OF DIFFERENT JAK TYROSINE KINASES IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 (HTLV-1) TAX PROTEIN OR VIRUS-TRANSFORMED CELLS [J].
XU, X ;
KANG, SH ;
HEIDENREICH, O ;
OKERHOLM, M ;
OSHEA, JJ ;
NERENBERG, MI .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (03) :1548-1555
[68]   ADULT T-CELL LEUKEMIA-LYMPHOMA [J].
YAMAGUCHI, K ;
TAKATSUKI, K .
BAILLIERES CLINICAL HAEMATOLOGY, 1993, 6 (04) :899-915
[69]   POLYCLONAL INTEGRATION OF HTLV-I PROVIRAL DNA IN LYMPHOCYTES FROM HTLV-I SEROPOSITIVE INDIVIDUALS - AN INTERMEDIATE STATE BETWEEN THE HEALTHY CARRIER STATE AND SMOLDERING ATL [J].
YAMAGUCHI, K ;
KIYOKAWA, T ;
NAKADA, K ;
YUL, LS ;
ASOU, N ;
ISHII, T ;
SANADA, I ;
SEIKI, M ;
YOSHIDA, M ;
MATUTES, E ;
CATOVSKY, D ;
TAKATSUKI, K .
BRITISH JOURNAL OF HAEMATOLOGY, 1988, 68 (02) :169-174
[70]  
YODOI J, 1985, J IMMUNOL, V134, P1623