Stat5 as a Hematopoietic Master Regulator for Differentiation and Neoplasia Development



Stat5 transcription factors have a crucial role in hematopoiesis from hematopoietic stem cells to fully differentiated cells. The individual contributions of Stat5a and Stat5b genes to the generation of hematopoietic cells and to their malignant transformation are subject of the following review. Absence of Stat5 proteins causes lymphopenia and Stat5 was recognized to be indispensable for the development of B-, T- and NK-cells. The few peripheral T-cells that develop in Stat5-deficient mice have an activated phenotype and these T-cells contribute to the development of autoimmunity. Moreover, deletion of Stat5 in myeloid cells causes myelodysplasia (red cell anemia and thrombocytopenia). In addition, generation and function of mast cells and eosinophils depends on Stat5. Impoartantly, Stat5 was found to be highly expressed and constitutively activated in many human hematopoietic neoplasms, where it regulates expression of genes controlling cell survival and cell cycle progression. Expression of Stat5 in hematopoietic neoplasms was both found to be elevated at the mRNA and protein level. Interestingly, higher Stat5 levels were linked with tyrosine kinase inhibitor drug resistance.


Acute Myeloid Leukemia Chronic Myeloid Leukemia Acute Myeloid Leukemia Patient Fetal Liver Cell Hematopoietic Neoplasm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Austrian Science Fund FWF grant SFB F28.


  1. Barnstein BO, Li G, Wang Z, Kennedy S, Chalfant C, Nakajima H, Bunting KD, Ryan JJ (2006) Stat5 expression is required for IgE-mediated mast cell function. J Immunol 177:3421–3426PubMedGoogle Scholar
  2. Birkenkamp KU, Geugien M, Lemmink HH, Kruijer W, Vellenga E (2001) Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 15:1923–1931PubMedCrossRefGoogle Scholar
  3. Bradley HL, Hawley TS, Bunting KD (2002) Cell intrinsic defects in cytokine responsiveness of STAT5-deficient hematopoietic stem cells. Blood 100:3983–3989PubMedCrossRefGoogle Scholar
  4. Buitenhuis M, Baltus B, Lammers JW, Coffer PJ, Koenderman L (2003) Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells. Blood 101:134–142PubMedCrossRefGoogle Scholar
  5. Bunting KD (2007) STAT5 signaling in normal and pathologic hematopoiesis. Front Biosci 12:2807–2820PubMedCrossRefGoogle Scholar
  6. Bunting KD, Bradley HL, Hawley TS, Moriggl R, Sorrentino BP, Ihle JN (2002) Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5. Blood 99:479–487PubMedCrossRefGoogle Scholar
  7. Burchill MA, Goetz CA, Prlic M, O’Neil JJ, Harmon IR, Bensinger SJ, Turka LA, Brennan P, Jameson SC, Farrar MA (2003) Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells. J Immunol 171:5853–5864PubMedGoogle Scholar
  8. Choudhary C, Olsen JV, Brandts C, Cox J, Reddy PN, Bohmer FD, Gerke V, Schmidt-Arras DE, Berdel WE, Muller-Tidow C, Mann M, Serve H (2009) Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 36:326–339PubMedCrossRefGoogle Scholar
  9. Chueh FY, Leong KF, Yu CL (2010) Mitochondrial translocation of signal transducer and activator of transcription 5 (STAT5) in leukemic T cells and cytokine-stimulated cells. Biochem Biophys Res Commun 402:778–783PubMedCrossRefGoogle Scholar
  10. Cui Y, Riedlinger G, Miyoshi K, Tang W, Li C, Deng CX, Robinson GW, Hennighausen L (2004) Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol Cell Biol 24:8037–8047PubMedCrossRefGoogle Scholar
  11. Dai X, Chen Y, Di L, Podd A, Li G, Bunting KD, Hennighausen L, Wen R, Wang D (2007) Stat5 is essential for early B cell development but not for B cell maturation and function. J Immunol 179:1068–1079PubMedGoogle Scholar
  12. De Keersmaecker K, Graux C, Odero MD, Mentens N, Somers R, Maertens J, Wlodarska I, Vandenberghe P, Hagemeijer A, Marynen P, Cools J (2005) Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14) (q34;q32). Blood 105:4849–4852PubMedCrossRefGoogle Scholar
  13. Dolznig H, Grebien F, Deiner EM, Stangl K, Kolbus A, Habermann B, Kerenyi MA, Kieslinger M, Moriggl R, Beug H, Mullner EW (2006) Erythroid progenitor renewal versus differentiation: genetic evidence for cell autonomous, essential functions of EpoR, Stat5 and the GR. Oncogene 25:2890–2900PubMedCrossRefGoogle Scholar
  14. Eckelhart E, Warsch W, Zebedin E, Simma O, Stoiber D, Kolbe T, Rulicke T, Mueller M, Casanova E, Sexl V (2011) A novel Ncr1-Cre mouse reveals the essential role of STAT5 for NK cell survival and development. Blood 117:1565–1573PubMedCrossRefGoogle Scholar
  15. Ermakova O, Piszczek L, Luciani L, Cavalli FM, Ferreira T, Farley D, Rizzo S, Paolicelli RC, Al-Banchaabouchi M, Nerlov C, Moriggl R, Luscombe NM, Gross C (2011) Sensitized phenotypic screening identifies gene dosage sensitive region on chromosome 11 that predisposes to disease in mice. EMBO Mol Med 3:50–66PubMedCrossRefGoogle Scholar
  16. Ferbeyre G, Moriggl R (2011) The role of Stat5 transcription factors as tumor suppressors or oncogenes. Biochim Biophys Acta 1815:104–114PubMedGoogle Scholar
  17. Fievez L, Desmet C, Henry E, Pajak B, Hegenbarth S, Garze V, Bex F, Jaspar F, Boutet P, Gillet L, Vanderplasschen A, Knolle PA, Leo O, Moser M, Lekeux P, Bureau F (2007) STAT5 is an ambivalent regulator of neutrophil homeostasis. PLoS One 2:e727PubMedCrossRefGoogle Scholar
  18. Friedbichler K, Kerenyi MA, Kovacic B, Li G, Hoelbl A, Yahiaoui S, Sexl V, Mullner EW, Fajmann S, Cerny-Reiterer S, Valent P, Beug H, Gouilleux F, Bunting KD, Moriggl R (2010) Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation. Blood 116:1548–1558PubMedCrossRefGoogle Scholar
  19. Giliani S, Mella P, Savoldi G, Mazzolari E (2005) Cytokine-mediated signalling and early defects in lymphoid development. Curr Opin Allergy Clin Immunol 5:519–524PubMedCrossRefGoogle Scholar
  20. Goetz CA, Harmon IR, O’Neil JJ, Burchill MA, Farrar MA (2004) STAT5 activation underlies IL7 receptor-dependent B cell development. J Immunol 172:4770–4778PubMedGoogle Scholar
  21. Grebien F, Kerenyi MA, Kovacic B, Kolbe T, Becker V, Dolznig H, Pfeffer K, Klingmuller U, Muller M, Beug H, Mullner EW, Moriggl R (2008) Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2. Blood 111:4511–4522PubMedCrossRefGoogle Scholar
  22. Guo L, Wei G, Zhu J, Liao W, Leonard WJ, Zhao K, Paul W (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci USA 106:13463–13468PubMedCrossRefGoogle Scholar
  23. Han L, Wierenga AT, Rozenveld-Geugien M, van de Lande K, Vellenga E, Schuringa JJ (2009) Single-cell STAT5 signal transduction profiling in normal and leukemic stem and progenitor cell populations reveals highly distinct cytokine responses. PLoS One 4:e7989PubMedCrossRefGoogle Scholar
  24. Hand TW, Cui W, Jung YW, Sefik E, Joshi NS, Chandele A, Liu Y, Kaech SM (2010) Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proc Natl Acad Sci USA 107:16601–16606PubMedCrossRefGoogle Scholar
  25. Heath C, Cross NC (2004) Critical role of STAT5 activation in transformation mediated by ZNF198-FGFR1. J Biol Chem 279:6666–6673PubMedCrossRefGoogle Scholar
  26. Heuser M, Sly LM, Argiropoulos B, Kuchenbauer F, Lai C, Weng A, Leung M, Lin G, Brookes C, Fung S, Valk PJ, Delwel R, Lowenberg B, Krystal G, Humphries RK (2009) Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal. Blood 114:3983–3993PubMedCrossRefGoogle Scholar
  27. Hirokawa S, Sato H, Kato I, Kudo A (2003) EBF-regulating Pax5 transcription is enhanced by STAT5 in the early stage of B cells. Eur J Immunol 33:1824–1829PubMedCrossRefGoogle Scholar
  28. Hoelbl A, Kovacic B, Kerenyi MA, Simma O, Warsch W, Cui Y, Beug H, Hennighausen L, Moriggl R, Sexl V (2006) Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood 107:4898–4906PubMedCrossRefGoogle Scholar
  29. Hwang ES, White IA, Ho IC (2002) An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines. Proc Natl Acad Sci USA 99:13026–13030PubMedCrossRefGoogle Scholar
  30. Imada K, Bloom ET, Nakajima H, Horvath-Arcidiacono JA, Udy GB, Davey HW, Leonard WJ (1998) Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity. J Exp Med 188:2067–2074PubMedCrossRefGoogle Scholar
  31. John S, Robbins CM, Leonard WJ (1996) An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein. EMBO J 15:5627–5635PubMedGoogle Scholar
  32. Kagami S, Nakajima H, Suto A, Hirose K, Suzuki K, Morita S, Kato I, Saito Y, Kitamura T, Iwamoto I (2001) Stat5a regulates T helper cell differentiation by several distinct mechanisms. Blood 97:2358–2365PubMedCrossRefGoogle Scholar
  33. Kang J, Der SD (2004) Cytokine functions in the formative stages of a lymphocyte’s life. Curr Opin Immunol 16:180–190PubMedCrossRefGoogle Scholar
  34. Kearney L, Gonzalez De Castro D, Yeung J, Procter J, Horsley SW, Eguchi-Ishimae M, Bateman CM, Anderson K, Chaplin T, Young BD, Harrison CJ, Kempski H, So CW, Ford AM, Greaves M (2009) Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood 113:646–648PubMedCrossRefGoogle Scholar
  35. Kelly J, Spolski R, Imada K, Bollenbacher J, Lee S, Leonard WJ (2003) A role for Stat5 in CD8+ T cell homeostasis. J Immunol 170:210–217PubMedGoogle Scholar
  36. Kerenyi MA, Grebien F, Gehart H, Schifrer M, Artaker M, Kovacic B, Beug H, Moriggl R, Mullner EW (2008) Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1. Blood 112:3878–3888PubMedCrossRefGoogle Scholar
  37. Kimura A, Rieger MA, Simone JM, Chen W, Wickre MC, Zhu BM, Hoppe PS, O’Shea JJ, Schroeder T, Hennighausen L (2009) The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis. Blood 114:4721–4728PubMedCrossRefGoogle Scholar
  38. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517PubMedCrossRefGoogle Scholar
  39. Lane SW, Fairbairn DJ, McCarthy C, Nandini A, Perry-Keene J, Kennedy GA (2008) Leukaemia cutis in atypical chronic myeloid leukaemia with a t(9;22) (p24;q11.2) leading to BCR-JAK2 fusion. Br J Haematol 142:503PubMedCrossRefGoogle Scholar
  40. Laurence A, Tato CM, Davidson TS, Kanno Y, Chen Z, Yao Z, Blank RB, Meylan F, Siegel R, Hennighausen L, Shevach EM, O’Shea JJ (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26:371–381PubMedCrossRefGoogle Scholar
  41. Levin SD, Koelling RM, Friend SL, Isaksen DE, Ziegler SF, Perlmutter RM, Farr AG (1999) Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+B cells in vitro and signals via a novel mechanism. J Immunol 162:677–683PubMedGoogle Scholar
  42. Li G, Wang Z, Zhang Y, Kang Z, Haviernikova E, Cui Y, Hennighausen L, Moriggl R, Wang D, Tse W, Bunting KD (2007) STAT5 requires the N-domain to maintain hematopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output. Exp Hematol 35:1684–1694PubMedCrossRefGoogle Scholar
  43. Li G, Miskimen KL, Wang Z, Xie XY, Tse W, Gouilleux F, Moriggl R, Bunting KD (2010) Effective targeting of STAT5-mediated survival in myeloproliferative neoplasms using ABT-737 combined with rapamycin. Leukemia 24:1397–1405PubMedCrossRefGoogle Scholar
  44. Liao W, Schones DE, Oh J, Cui Y, Cui K, Roh TY, Zhao K, Leonard WJ (2008) Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. Nat Immunol 9:1288–1296PubMedCrossRefGoogle Scholar
  45. Liu F, Kunter G, Krem MM, Eades WC, Cain JA, Tomasson MH, Hennighausen L, Link DC (2008) Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. J Clin Invest 118:946–955PubMedGoogle Scholar
  46. Malin S, McManus S, Busslinger M (2010a) STAT5 in B cell development and leukemia. Curr Opin Immunol 22:168–176PubMedCrossRefGoogle Scholar
  47. Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, Strasser A, Busslinger M (2010b) Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol 11:171–179PubMedCrossRefGoogle Scholar
  48. Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, Ihle JN (1999) Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10:249–259PubMedCrossRefGoogle Scholar
  49. Moriggl R, Sexl V, Kenner L, Duntsch C, Stangl K, Gingras S, Hoffmeyer A, Bauer A, Piekorz R, Wang D, Bunting KD, Wagner EF, Sonneck K, Valent P, Ihle JN, Beug H (2005) Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 7:87–99PubMedCrossRefGoogle Scholar
  50. Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen IM, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP, Willman CL (2009) JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 106:9414–9418PubMedCrossRefGoogle Scholar
  51. Nicot C, Mulloy JC, Ferrari MG, Johnson JM, Fu K, Fukumoto R, Trovato R, Fullen J, Leonard WJ, Franchini G (2001) HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells. Blood 98:823–829PubMedCrossRefGoogle Scholar
  52. Oboki K, Ohno T, Kajiwara N, Saito H, Nakae S (2010) IL-33 and IL-33 receptors in host defense and diseases. Allergol Int 59:143–160PubMedCrossRefGoogle Scholar
  53. Osborne LC, Abraham N (2010) Regulation of memory T cells by gammac cytokines. Cytokine 50:105–113PubMedCrossRefGoogle Scholar
  54. Park JH, Adoro S, Guinter T, Erman B, Alag AS, Catalfamo M, Kimura MY, Cui YZ, Lucas PJ, Gress RE, Kubo M, Hennighausen L, Feigenbaum L, Singer A (2010) Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat Immunol 11:257, U210PubMedCrossRefGoogle Scholar
  55. Pugliese-Pires PN, Tonelli CA, Dora JM, Silva PC, Czepielewski M, Simoni G, Arnhold IJ, Jorge AA (2010) A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblings. Eur J Endocrinol 163:349–355PubMedCrossRefGoogle Scholar
  56. Rochman Y, Kashyap M, Robinson GW, Sakamoto K, Gomez-Rodriguez J, Wagner KU, Leonard WJ (2010) Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling. Proc Natl Acad Sci USA 107:19455–19460PubMedCrossRefGoogle Scholar
  57. Scheeren FA, Naspetti M, Diehl S, Schotte R, Nagasawa M, Wijnands E, Gimeno R, Vyth-Dreese FA, Blom B, Spits H (2005) STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression. Nat Immunol 6:303–313PubMedCrossRefGoogle Scholar
  58. Schepers H, van Gosliga D, Wierenga AT, Eggen BJ, Schuringa JJ, Vellenga E (2007) STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells. Blood 110:2880–2888PubMedCrossRefGoogle Scholar
  59. Scherr M, Chaturvedi A, Battmer K, Dallmann I, Schultheis B, Ganser A, Eder M (2006) Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 107:3279–3287PubMedCrossRefGoogle Scholar
  60. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, Futreal PA, Erber WN, McMullin MF, Harrison CN, Warren AJ, Gilliland DG, Lodish HF, Green AR (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356:459–468PubMedCrossRefGoogle Scholar
  61. Sexl V, Piekorz R, Moriggl R, Rohrer J, Brown MP, Bunting KD, Rothammer K, Roussel MF, Ihle JN (2000) Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5. Blood 96:2277–2283PubMedGoogle Scholar
  62. Shelburne CP, McCoy ME, Piekorz R, Sexl V, Roh KH, Jacobs-Helber SM, Gillespie SR, Bailey DP, Mirmonsef P, Mann MN, Kashyap M, Wright HV, Chong HJ, Bouton LA, Barnstein B, Ramirez CD, Bunting KD, Sawyer S, Lantz CS, Ryan JJ (2003) Stat5 expression is critical for mast cell development and survival. Blood 102:1290–1297PubMedCrossRefGoogle Scholar
  63. Shide K, Shimoda HK, Kumano T, Karube K, Kameda T, Takenaka K, Oku S, Abe H, Katayose KS, Kubuki Y, Kusumoto K, Hasuike S, Tahara Y, Nagata K, Matsuda T, Ohshima K, Harada M, Shimoda K (2008) Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. Leukemia 22:87–95PubMedCrossRefGoogle Scholar
  64. Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, Blasiak J, Fishel R, Skorski T (2002) Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol 22:4189–4201PubMedCrossRefGoogle Scholar
  65. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93:841–850PubMedCrossRefGoogle Scholar
  66. Tomasson MH, Sternberg DW, Williams IR, Carroll M, Cain D, Aster JC, Ilaria RL Jr, Van Etten RA, Gilliland DG (2000) Fatal myeloproliferation, induced in mice by TEL/PDGFbetaR expression, depends on PDGFbetaR tyrosines 579/581. J Clin Invest 105:423–432PubMedCrossRefGoogle Scholar
  67. Valent P, Akin C, Sperr WR, Horny HP, Metcalfe DD (2003) Mast cell proliferative disorders: current view on variants recognized by the World Health Organization. Hematol Oncol Clin North Am 17:1227–1241PubMedCrossRefGoogle Scholar
  68. Vermeer MH, van Doorn R, Dijkman R, Mao X, Whittaker S, van Voorst Vader PC, Gerritsen MJ, Geerts ML, Gellrich S, Soderberg O, Leuchowius KJ, Landegren U, Out-Luiting JJ, Knijnenburg J, Ijszenga M, Szuhai K, Willemze R, Tensen CP (2008) Novel and highly recurrent chromosomal alterations in Sezary syndrome. Cancer Res 68:2689–2698PubMedCrossRefGoogle Scholar
  69. Vranjkovic A, Crawley AM, Patey A, Angel JB (2010) IL-7-dependent STAT-5 activation and CD8+ T cell proliferation are impaired in HIV infection. J Leukoc Biol 89:499–506PubMedCrossRefGoogle Scholar
  70. Walters DK, Goss VL, Stoffregen EP, Gu TL, Lee K, Nardone J, McGreevey L, Heinrich MC, Deininger MW, Polakiewicz R, Druker BJ (2006a) Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes. Leuk Res 30:1097–1104PubMedCrossRefGoogle Scholar
  71. Walters DK, Mercher T, Gu TL, O’Hare T, Tyner JW, Loriaux M, Goss VL, Lee KA, Eide CA, Wong MJ, Stoffregen EP, McGreevey L, Nardone J, Moore SA, Crispino J, Boggon TJ, Heinrich MC, Deininger MW, Polakiewicz RD, Gilliland DG, Druker BJ (2006b) Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 10:65–75PubMedCrossRefGoogle Scholar
  72. Warsch W, Kollmann K, Eckelhart E, Fajmann S, Cerny-Reiterer S, Holbl A, Gleixner KV, Dworzak M, Mayerhofer M, Hoermann G, Herrmann H, Sillaber C, Egger G, Valent P, Moriggl R, Sexl V (2011) High STAT5 levels mediate imatinib resistance and indicate disease progression in chronic myeloid leukemia. Blood 117:3409–3420PubMedCrossRefGoogle Scholar
  73. Wohlmann A, Sebastian K, Borowski A, Krause S, Friedrich K (2010) Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function. Biol Chem 391:181–186PubMedCrossRefGoogle Scholar
  74. Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR, Hirahara K, Sun HW, Wei L, Vahedi G, Kanno Y, O’Shea JJ, Laurence A (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12:247–254PubMedCrossRefGoogle Scholar
  75. Yao Z, Cui Y, Watford WT, Bream JH, Yamaoka K, Hissong BD, Li D, Durum SK, Jiang Q, Bhandoola A, Hennighausen L, O’Shea JJ (2006) Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci USA 103:1000–1005PubMedCrossRefGoogle Scholar
  76. Yao Z, Kanno Y, Kerenyi M, Stephens G, Durant L, Watford WT, Laurence A, Robinson GW, Shevach EM, Moriggl R, Hennighausen L, Wu C, O’Shea JJ (2007) Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109:4368–4375PubMedCrossRefGoogle Scholar
  77. Yoshimoto G, Miyamoto T, Jabbarzadeh-Tabrizi S, Iino T, Rocnik JL, Kikushige Y, Mori Y, Shima T, Iwasaki H, Takenaka K, Nagafuji K, Mizuno S, Niiro H, Gilliland GD, Akashi K (2009) FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation. Blood 114:5034–5043PubMedCrossRefGoogle Scholar
  78. Yu CR, Ortaldo JR, Curiel RE, Young HA, Anderson SK, Gosselin P (1999) Role of a STAT binding site in the regulation of the human perforin promoter. J Immunol 162:2785–2790PubMedGoogle Scholar
  79. Zhang Q, Nowak I, Vonderheid EC, Rook AH, Kadin ME, Nowell PC, Shaw LM, Wasik MA (1996) Activation of Jak/STAT proteins involved in signal transduction pathway mediated by receptor for interleukin 2 in malignant T lymphocytes derived from cutaneous anaplastic large T-cell lymphoma and Sezary syndrome. Proc Natl Acad Sci USA 93:9148–9153PubMedCrossRefGoogle Scholar
  80. Zhang Q, Wang HY, Liu X, Wasik MA (2007) STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression. Nat Med 13:1341–1348PubMedCrossRefGoogle Scholar
  81. Zhu J (2010) Transcriptional regulation of Th2 cell differentiation. Immunol Cell Biol 88:244–249PubMedCrossRefGoogle Scholar
  82. Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112:1557–1569PubMedCrossRefGoogle Scholar
  83. Zhu Y, Chen L, Huang Z, Alkan S, Bunting KD, Wen R, Wang D, Huang H (2004) Cutting edge: IL-5 primes Th2 cytokine-producing capacity in eosinophils through a STAT5-dependent mechanism. J Immunol 173:2918–2922PubMedGoogle Scholar
  84. Zwirner NW, Domaica CI (2010) Cytokine regulation of natural killer cell effector functions. Biofactors 36:274–288PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  1. 1.Ludwig Boltzmann Institute for Cancer Research (LBI-CR)ViennaAustria

Personalised recommendations