SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function

被引：10

作者：

Hansen, N. ^{[1
]}

Agerstam, H. ^{[1
]}

Wahlestedt, M. ^{[2
]}

Landberg, N. ^{[1
]}

Askmyr, M. ^{[1
]}

Ehinger, M. ^{[3
]}

Rissler, M. ^{[1
]}

Lilljebjorn, H. ^{[1
]}

Johnels, P. ^{[1
]}

Ishiko, J. ^{[4
]}

Melo, J. V. ^{[4
,5
]}

Alexander, W. S. ^{[6
,7
]}

Bryder, D. ^{[2
]}

Jaras, M. ^{[1
]}

Fioretos, T. ^{[1
]}

机构：

[1] Lund Univ, Dept Clin Genet, Univ & Reg Labs, Lund, Sweden

[2] Lund Univ, Dept Expt Med, Immunol Sect, Lund, Sweden

[3] Univ Lund Hosp, Dept Pathol, S-22185 Lund, Sweden

[4] Ctr Canc Biol, Dept Haematol, Adelaide, SA, Australia

[5] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England

[6] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Parkville, Vic 3050, Australia

[7] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia

来源：

LEUKEMIA | 2013年 / 27卷 / 01期

基金：

瑞典研究理事会; 英国医学研究理事会;

关键词：

CML; BCR/ABL1; SOCS2; HSC; STAT5; phosphorylation; BCR-ABL; TYROSINE PHOSPHORYLATION; ALOX5; GENE; EXPRESSION; SUPPRESSOR; GROWTH; MICE; PROTEIN; FAMILY; STAT5;

D O I：

10.1038/leu.2012.169

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Suppressor of cytokine signaling 2 (SOCS2) is known as a feedback inhibitor of cytokine signaling and is highly expressed in primary bone marrow (BM) cells from patients with chronic myeloid leukemia (CML). However, it has not been established whether SOCS2 is involved in CML, caused by the BCR/ABL1 fusion gene, or important for normal hematopoietic stem cell (HSC) function. In this study, we demonstrate that although Socs2 was found to be preferentially expressed in long-term HSCs, Socs2-deficient HSCs were indistinguishable from wild-type HSCs when challenged in competitive BM transplantation experiments. Furthermore, by using a retroviral BCR/ABL1-induced mouse model of CML, we demonstrate that SOCS2 is dispensable for the induction and propagation of the disease, suggesting that the SOCS2-mediated feedback regulation of the JAK/STAT pathway is deficient in BCR/ABL1-induced CML. Leukemia (2013) 27, 130-135; doi:10.1038/leu.2012.169

引用

页码：130 / 135

页数：6

共 39 条

[31] Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions [J].

Rico-Bautista, Elizabeth ;

Flores-Morales, Amilcar ;

Fernandez-Perez, Leandro .

CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (06) :431-439

[32] Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia [J].

Samanta, A. ;

Perazzona, B. ;

Chakraborty, S. ;

Sun, X. ;

Modi, H. ;

Bhatia, R. ;

Priebe, W. ;

Arlinghaus, R. .

LEUKEMIA, 2011, 25 (03) :463-472

[33] Overexpression of SOCS-2 in advanced stages of chronic myeloid leukemia:: possible inadequacy of a negative feedback mechanism [J].

Schultheis, B ;

Carapeti-Marootian, M ;

Hochhaus, A ;

Weisser, A ;

Goldman, JM ;

Melo, JV .

BLOOD, 2002, 99 (05) :1766-1775

[34]

Shuai K, 1996, ONCOGENE, V13, P247

[35] A family of cytokine-inducible inhibitors of signalling [J].

Starr, R ;

Willson, TA ;

Viney, EM ;

Murray, LJL ;

Rayner, JR ;

Jenkins, BJ ;

Gonda, TJ ;

Alexander, WS ;

Metcalf, D ;

Nicola, NA ;

Hilton, DJ .

NATURE, 1997, 387 (6636) :917-921

[36] SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation [J].

Tannahill, GM ;

Elliott, J ;

Barry, AC ;

Hibbert, L ;

Cacalano, NA ;

Johnston, JA .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (20) :9115-9126

[37] A model-based background adjustment for oligonucleotide expression arrays [J].

Wu, ZJ ;

Irizarry, RA ;

Gentleman, R ;

Martinez-Murillo, F ;

Spencer, F .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2004, 99 (468) :909-917

[38] Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation [J].

Xie, SH ;

Wang, Y ;

Liu, JX ;

Sun, T ;

Wilson, MB ;

Smithgall, TE ;

Arlinghaus, RB .

ONCOGENE, 2001, 20 (43) :6188-6195

[39] Gene expression profiling of CD34+cells identifies a molecular signature of chronic myeloid leukemia blast crisis [J].

Zheng, C. ;

Li, L. ;

Haak, M. ;

Brors, B. ;

Frank, O. ;

Giehl, M. ;

Fabarius, A. ;

Schatz, M. ;

Weisser, A. ;

Lorentz, C. ;

Gretz, N. ;

Hehlmann, R. ;

Hochhaus, A. ;

Seifarth, W. .

LEUKEMIA, 2006, 20 (06) :1028-1034

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