Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma

Jeong Hee Cho, G. Z. Rassidakis, H. M. Amin, P. Tsioli, K. Spurgers, Y. K. Remache, Francisco Vega, A. H. Goy, F. Gilles, L. Jeffrey Medeiros

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK + ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK + tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK + tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.

Original languageEnglish
Pages (from-to)1872-1878
Number of pages7
JournalLeukemia
Volume18
Issue number11
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

Anaplastic Large-Cell Lymphoma
STAT3 Transcription Factor
Cytokines
Janus Kinase 3
Neoplasms
Cell Line
anaplastic lymphoma kinase
Alternative Splicing
Oligonucleotide Array Sequence Analysis
Transcriptional Activation
Up-Regulation
Down-Regulation
Western Blotting
Immunohistochemistry

Keywords

  • ALCL
  • ALK
  • JAK3
  • SOCS3
  • STAT3

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Cho, J. H., Rassidakis, G. Z., Amin, H. M., Tsioli, P., Spurgers, K., Remache, Y. K., ... Medeiros, L. J. (2004). Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. Leukemia, 18(11), 1872-1878. https://doi.org/10.1038/sj.leu.2403495

Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. / Cho, Jeong Hee; Rassidakis, G. Z.; Amin, H. M.; Tsioli, P.; Spurgers, K.; Remache, Y. K.; Vega, Francisco; Goy, A. H.; Gilles, F.; Medeiros, L. Jeffrey.

In: Leukemia, Vol. 18, No. 11, 01.11.2004, p. 1872-1878.

Research output: Contribution to journalArticle

Cho, JH, Rassidakis, GZ, Amin, HM, Tsioli, P, Spurgers, K, Remache, YK, Vega, F, Goy, AH, Gilles, F & Medeiros, LJ 2004, 'Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma', Leukemia, vol. 18, no. 11, pp. 1872-1878. https://doi.org/10.1038/sj.leu.2403495
Cho JH, Rassidakis GZ, Amin HM, Tsioli P, Spurgers K, Remache YK et al. Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. Leukemia. 2004 Nov 1;18(11):1872-1878. https://doi.org/10.1038/sj.leu.2403495
Cho, Jeong Hee ; Rassidakis, G. Z. ; Amin, H. M. ; Tsioli, P. ; Spurgers, K. ; Remache, Y. K. ; Vega, Francisco ; Goy, A. H. ; Gilles, F. ; Medeiros, L. Jeffrey. / Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma. In: Leukemia. 2004 ; Vol. 18, No. 11. pp. 1872-1878.
@article{a10526798c224c8d91a8c0e9ee8d6db2,
title = "Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma",
abstract = "Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK + ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75{\%}) ALK + tumors were SOCS3 positive and eight (67{\%}) coexpressed pSTAT3. In comparison, 18 of 25 (72{\%}) ALK-tumors were SOCS3 positive and seven (28{\%}) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK + tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.",
keywords = "ALCL, ALK, JAK3, SOCS3, STAT3",
author = "Cho, {Jeong Hee} and Rassidakis, {G. Z.} and Amin, {H. M.} and P. Tsioli and K. Spurgers and Remache, {Y. K.} and Francisco Vega and Goy, {A. H.} and F. Gilles and Medeiros, {L. Jeffrey}",
year = "2004",
month = "11",
day = "1",
doi = "10.1038/sj.leu.2403495",
language = "English",
volume = "18",
pages = "1872--1878",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Suppressor of cytokine signaling 3 expression in anaplastic large cell lymphoma

AU - Cho, Jeong Hee

AU - Rassidakis, G. Z.

AU - Amin, H. M.

AU - Tsioli, P.

AU - Spurgers, K.

AU - Remache, Y. K.

AU - Vega, Francisco

AU - Goy, A. H.

AU - Gilles, F.

AU - Medeiros, L. Jeffrey

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK + ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK + tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK + tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.

AB - Using a cDNA microarray, we found that suppressor of cytokine signaling 3 (SOCS3) is highly expressed in anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) cell lines. As SOCS3 is induced by activated signal transducer and activator of transcription 3 (STAT3), and ALK activates STAT3, we hypothesized that SOCS3 may play a role in ALK + ALCL pathogenesis via the Janus kinase 3 (JAK3)-STAT3 pathway. Using ALCL cell lines, we show by coimmunoprecipitation experiments that SOCS3 physically binds with JAK3 in vitro, and that JAK3 inhibition by WHI-P154 downregulates SOCS3 expression. Western blot analysis confirmed expression of SOCS3 and also showed coexpression of phosphorylated (activated) STAT3 (pSTAT3). Direct sequencing of the SOCS3 gene showed no mutations or alternative splicing. In ALCL tumors that were assessed by immunohistochemistry, nine of 12 (75%) ALK + tumors were SOCS3 positive and eight (67%) coexpressed pSTAT3. In comparison, 18 of 25 (72%) ALK-tumors were SOCS3 positive and seven (28%) coexpressed pSTAT3. These results show that SOCS3 is overexpressed in ALCL, attributable to JAK3-STAT3 activation and likely related to ALK in ALK + tumors. However, SOCS3 is also expressed in tumors that lack STAT3 and ALK suggesting alternative mechanisms of upregulation.

KW - ALCL

KW - ALK

KW - JAK3

KW - SOCS3

KW - STAT3

UR - http://www.scopus.com/inward/record.url?scp=8844233462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8844233462&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2403495

DO - 10.1038/sj.leu.2403495

M3 - Article

VL - 18

SP - 1872

EP - 1878

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 11

ER -