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

[1] Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice [J].

Agerstam, Helena ;

Jaras, Marcus ;

Andersson, Anna ;

Johnels, Petra ;

Hansen, Nils ;

Lassen, Carin ;

Rissler, Marianne ;

Gisselsson, David ;

Olofsson, Tor ;

Richter, Johan ;

Fan, Xiaolong ;

Ehinger, Mats ;

Fioretos, Thoas .

BLOOD, 2010, 116 (12) :2103-2111

[2] The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia [J].

Chen, Yaoyu ;

Li, Dongguang ;

Li, Shaoguang .

CELL CYCLE, 2009, 8 (21) :3488-3492

[3] Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia [J].

Chen, Yaoyu ;

Hu, Yiguo ;

Zhang, Haojian ;

Peng, Cong ;

Li, Shaoguang .

NATURE GENETICS, 2009, 41 (07) :783-U37

[4] STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver [J].

Davey, HW ;

McLachlan, MJ ;

Wilkins, RJ ;

Hilton, DJ ;

Adams, TE .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1999, 158 (1-2) :111-116

[5] c-CBL is not required for leukemia induction by Bcr-Abl in mice [J].

Dinulescu, DM ;

Wood, LJ ;

Shen, L ;

Loriaux, M ;

Corless, CL ;

Gross, AW ;

Ren, RB ;

Deininger, MWN ;

Druker, BJ .

ONCOGENE, 2003, 22 (55) :8852-8860

[6] A new protein containing an SH2 domain that inhibits JAK kinases [J].

Endo, TA ;

Masuhara, M ;

Yokouchi, M ;

Suzuki, R ;

Sakamoto, H ;

Mitsui, K ;

Matsumoto, A ;

Tanimura, S ;

Ohtsubo, M ;

Misawa, H ;

Miyazaki, T ;

Leonor, N ;

Taniguchi, T ;

Fujita, T ;

Kanakura, Y ;

Komiya, S ;

Yoshimura, A .

NATURE, 1997, 387 (6636) :921-924

[7] Stem cell gene expression programs influence clinical outcome in human leukemia [J].

Eppert, Kolja ;

Takenaka, Katsuto ;

Lechman, Eric R. ;

Waldron, Levi ;

Nilsson, Bjoern ;

van Galen, Peter ;

Metzeler, Klaus H. ;

Poeppl, Armando ;

Ling, Vicki ;

Beyene, Joseph ;

Canty, Angelo J. ;

Danska, Jayne S. ;

Bohlander, Stefan K. ;

Buske, Christian ;

Minden, Mark D. ;

Golub, Todd R. ;

Jurisica, Igor ;

Ebert, Benjamin L. ;

Dick, John E. .

NATURE MEDICINE, 2011, 17 (09) :1086-U91

[8] Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b) [J].

Greenhalgh, CJ ;

Bertolino, P ;

Asa, SL ;

Metcalf, D ;

Corbin, JE ;

Adams, TE ;

Davey, HW ;

Nicola, NA ;

Hilton, DJ ;

Alexander, WS .

MOLECULAR ENDOCRINOLOGY, 2002, 16 (06) :1394-1406

[9] Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling [J].

Greenhalgh, CJ ;

Metcalf, D ;

Thaus, AL ;

Corbin, JE ;

Uren, R ;

Morgan, PO ;

Fabri, LJ ;

Zhang, JG ;

Martin, HM ;

Willson, TA ;

Billestrup, N ;

Nicola, NA ;

Baca, M ;

Alexander, WS ;

Hilton, DJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) :40181-40184

[10]

HAWLEY RG, 1994, GENE THER, V1, P136

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