Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels

REFERENCES

• Argiropoulos, B., and R. K. Humphries. 2007. Hox genes in hematopoiesis and leukemogenesis. Oncogene 26:6766–6776.
   PubMed Web of Science ®Google Scholar
• Azam, M., H. Erdjument-Bromage, B. L. Kreider, M. Xia, F. Quelle, R. Basu, C. Saris, P. Tempst, J. N. Ihle, and C. Schindler. 1995. Interleukin-3 signals through multiple isoforms of Stat5. EMBO J. 14:1402–1411.
   PubMed Web of Science ®Google Scholar
• Barjesteh van Waalwijk van Doorn-Khosrovani, S., C. Erpelink, J. Meijer, S. van Oosterhoud, W. L. van Putten, P. J. Valk, H. Berna Beverloo, D. G. Tenen, B. Lowenberg, and R. Delwel. 2003. Biallelic mutations in the CEBPA gene and low CEBPA expression levels as prognostic markers in intermediate-risk AML. Hematol. J. 4:31–40.
   PubMedGoogle Scholar
• Birkenkamp, K. U., M. Geugien, H. H. Lemmink, W. Kruijer, and E. Vellenga. 2001. Regulation of constitutive STAT5 phosphorylation in acute myeloid leukemia blasts. Leukemia 15:1923–1931.
   PubMed Web of Science ®Google Scholar
• Bradley, H. L., C. Couldrey, and K. D. Bunting. 2004. Hematopoietic-repopulating defects from STAT5-deficient bone marrow are not fully accounted for by loss of thrombopoietin responsiveness. Blood 103:2965–2972.
   PubMedGoogle Scholar
• Bradley, H. L., T. S. Hawley, and K. D. Bunting. 2002. Cell intrinsic defects in cytokine responsiveness of STAT5-deficient hematopoietic stem cells. Blood 100:3983–3989.
   PubMedGoogle Scholar
• Buitenhuis, M., B. Baltus, J. W. Lammers, P. J. Coffer, and L. Koenderman. 2003. Signal transducer and activator of transcription 5a (STAT5a) is required for eosinophil differentiation of human cord blood-derived CD34+ cells. Blood 101:134–142.
   PubMed Web of Science ®Google Scholar
• Bunting, K. D. 2007. STAT5 signaling in normal and pathologic hematopoiesis. Front. Biosci. 12:2807–2820.
   PubMedGoogle Scholar
• Bunting, K. D., H. L. Bradley, T. S. Hawley, R. Moriggl, B. P. Sorrentino, and J. N. Ihle. 2002. Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5. Blood 99:479–487.
   PubMedGoogle Scholar
• Carlesso, N., D. A. Frank, and J. D. Griffin. 1996. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J. Exp. Med. 183:811–820.
   PubMed Web of Science ®Google Scholar
• Chadwick, N., M. C. Nostro, M. Baron, R. Mottram, G. Brady, and A. M. Buckle. 2007. Notch signaling induces apoptosis in primary human CD34+ hematopoietic progenitor cells. Stem Cells 25:203–210.
   PubMed Web of Science ®Google Scholar
• Chapiro, E., L. Russell, I. Radford-Weiss, C. Bastard, M. Lessard, S. Struski, H. Cave, S. Fert-Ferrer, C. Barin, O. Maarek, V. la-Valle, J. C. Strefford, R. Berger, C. J. Harrison, O. A. Bernard, and F. Nguyen-Khac. 2006. Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia. Blood 108:3560–3563.
   PubMed Web of Science ®Google Scholar
• Chung, K. Y., G. Morrone, J. J. Schuringa, B. Wong, D. C. Dorn, and M. A. Moore. 2005. Enforced expression of an Flt3 internal tandem duplication in human CD34+ cells confers properties of self-renewal and enhanced erythropoiesis. Blood 105:77–84.
   PubMedGoogle Scholar
• de Jonge, H. J., R. S. Fehrmann, E. S. de Bont, R. M. Hofstra, F. Gerbens, W. A. Kamps, E. G. de Vries, A. G. van der Zee, G. J. te Meerman, and A. ter Elst. 2007. Evidence based selection of housekeeping genes. PLoS One 2:e898.
   PubMed Web of Science ®Google Scholar
• Fatrai, S., H. Schepers, H. Tadema, S. Daenen, E. Vellenga, and J. J. Schuringa. Mucin1 expression is enriched in the human stem cell fraction of cord blood and is up-regulated in majority of the AML cases. Exp. Hematol., in press.
   Google Scholar
• Gouilleux-Gruart, V., F. Gouilleux, C. Desaint, J. F. Claisse, J. C. Capiod, J. Delobel, R. Weber-Nordt, I. Dusanter-Fourt, F. Dreyfus, B. Groner, and L. Prin. 1996. STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. Blood 87:1692–1697.
   PubMed Web of Science ®Google Scholar
• Grebien, F., M. A. Kerenyi, B. Kovacic, T. Kolbe, V. Becker, H. Dolznig, K. Pfeffer, U. Klingmuller, M. Muller, H. Beug, E. W. Mullner, and R. Moriggl. 2008. Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2. Blood 111:4511–4522.
   PubMed Web of Science ®Google Scholar
• Guentchev, M., and R. D. McKay. 2006. Notch controls proliferation and differentiation of stem cells in a dose-dependent manner. Eur. J. Neurosci. 23:2289–2296.
   PubMed Web of Science ®Google Scholar
• Harir, N., C. Pecquet, M. Kerenyi, K. Sonneck, B. Kovacic, R. Nyga, M. Brevet, I. Dhennin, V. Gouilleux-Gruart, H. Beug, P. Valent, K. Lassoued, R. Moriggl, and F. Gouilleux. 2007. Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias. Blood 109:1678–1686.
   PubMed Web of Science ®Google Scholar
• Hennighausen, L., and G. W. Robinson. 2008. Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev. 22:711–721.
   PubMed Web of Science ®Google Scholar
• Hoelbl, A., B. Kovacic, M. A. Kerenyi, O. Simma, W. Warsch, Y. Cui, H. Beug, L. Hennighausen, R. Moriggl, and V. Sexl. 2006. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood 107:4898–4906.
   PubMedGoogle Scholar
• Hurt, E. M., A. Wiestner, A. Rosenwald, A. L. Shaffer, E. Campo, T. Grogan, P. L. Bergsagel, W. M. Kuehl, and L. M. Staudt. 2004. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer Cell 5:191–199.
   PubMed Web of Science ®Google Scholar
• Ihle, J. N. 2001. The Stat family in cytokine signaling. Curr. Opin. Cell Biol. 13:211–217.
   PubMed Web of Science ®Google Scholar
• Ilaria, R. L., Jr., and R. A. Van Etten. 1996. P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J. Biol. Chem. 271:31704–31710.
   PubMed Web of Science ®Google Scholar
• Iwasaki, H., C. Somoza, H. Shigematsu, E. A. Duprez, J. Iwasaki-Arai, S. Mizuno, Y. Arinobu, K. Geary, P. Zhang, T. Dayaram, M. L. Fenyus, S. Elf, S. Chan, P. Kastner, C. S. Huettner, R. Murray, D. G. Tenen, and K. Akashi. 2005. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation. Blood 106:1590–1600.
   PubMed Web of Science ®Google Scholar
• Kato, Y., A. Iwama, Y. Tadokoro, K. Shimoda, M. Minoguchi, S. Akira, M. Tanaka, A. Miyajima, T. Kitamura, and H. Nakauchi. 2005. Selective activation of STAT5 unveils its role in stem cell self-renewal in normal and leukemic hematopoiesis. J. Exp. Med. 202:169–179.
   PubMedGoogle Scholar
• Kirstetter, P., K. Anderson, B. T. Porse, S. E. Jacobsen, and C. Nerlov. 2006. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat. Immunol. 7:1048–1056.
   PubMed Web of Science ®Google Scholar
• Lacout, C., D. F. Pisani, M. Tulliez, F. M. Gachelin, W. Vainchenker, and J. L. Villeval. 2006. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 108:1652–1660.
   PubMed Web of Science ®Google Scholar
• Li, G., Z. Wang, Y. Zhang, Z. Kang, E. Haviernikova, Y. Cui, L. Hennighausen, R. Moriggl, D. Wang, W. Tse, and K. D. Bunting. 2007. STAT5 requires the N-domain to maintain hematopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output. Exp. Hematol. 35:1684–1694.
   PubMedGoogle Scholar
• Mallette, F. A., M. F. Gaumont-Leclerc, and G. Ferbeyre. 2007. The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev. 21:43–48.
   PubMed Web of Science ®Google Scholar
• Moore, M. A., D. C. Dorn, J. J. Schuringa, K. Y. Chung, and G. Morrone. 2007. Constitutive activation of Flt3 and STAT5A enhances self-renewal and alters differentiation of hematopoietic stem cells. Exp. Hematol. 35:105–116.
   PubMed Web of Science ®Google Scholar
• Moriggl, R., V. Sexl, L. Kenner, C. Duntsch, K. Stangl, S. Gingras, A. Hoffmeyer, A. Bauer, R. Piekorz, D. Wang, K. D. Bunting, E. F. Wagner, K. Sonneck, P. Valent, J. N. Ihle, and H. Beug. 2005. Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 7:87–99.
   PubMed Web of Science ®Google Scholar
• Mui, A. L., H. Wakao, A. M. O'Farrell, N. Harada, and A. Miyajima. 1995. Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J. 14:1166–1175.
   PubMed Web of Science ®Google Scholar
• Murphy, M. J., A. Wilson, and A. Trumpp. 2005. More than just proliferation: Myc function in stem cells. Trends Cell Biol. 15:128–137.
   PubMedGoogle Scholar
• Nosaka, T., T. Kawashima, K. Misawa, K. Ikuta, A. L. Mui, and T. Kitamura. 1999. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J. 18:4754–4765.
   PubMed Web of Science ®Google Scholar
• Pabst, T., B. U. Mueller, P. Zhang, H. S. Radomska, S. Narravula, S. Schnittger, G. Behre, W. Hiddemann, and D. G. Tenen. 2001. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPα), in acute myeloid leukemia. Nat. Genet. 27:263–270.
   PubMed Web of Science ®Google Scholar
• Pallard, C., F. Gouilleux, L. Benit, L. Cocault, M. Souyri, D. Levy, B. Groner, S. Gisselbrecht, and I. Dusanter-Fourt. 1995. Thrombopoietin activates a STAT5-like factor in hematopoietic cells. EMBO J. 14:2847–2856.
   PubMed Web of Science ®Google Scholar
• Pallard, C., F. Gouilleux, M. Charon, B. Groner, S. Gisselbrecht, and I. Dusanter-Fourt. 1995. Interleukin-3, erythropoietin, and prolactin activate a STAT5-like factor in lymphoid cells. J. Biol. Chem. 270:15942–15945.
   PubMed Web of Science ®Google Scholar
• Paukku, K., and O. Silvennoinen. 2004. STATs as critical mediators of signal transduction and transcription: lessons learned from STAT5. Cytokine Growth Factor Rev. 15:435–455.
   PubMed Web of Science ®Google Scholar
• Radomska, H. S., D. S. Basseres, R. Zheng, P. Zhang, T. Dayaram, Y. Yamamoto, D. W. Sternberg, N. Lokker, N. A. Giese, S. K. Bohlander, S. Schnittger, M. H. Delmotte, R. J. Davis, D. Small, W. Hiddemann, D. G. Gilliland, and D. G. Tenen. 2006. Block of C/EBP alpha function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations. J. Exp. Med. 203:371–381.
   PubMed Web of Science ®Google Scholar
• Reya, T., A. W. Duncan, L. Ailles, J. Domen, D. C. Scherer, K. Willert, L. Hintz, R. Nusse, and I. L. Weissman. 2003. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414.
   PubMed Web of Science ®Google Scholar
• Rosenbauer, F., K. Wagner, J. L. Kutok, H. Iwasaki, M. M. Le Beau, Y. Okuno, K. Akashi, S. Fiering, and D. G. Tenen. 2004. Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1. Nat. Genet. 36:624–630.
   PubMed Web of Science ®Google Scholar
• Ryan, J. J., H. Huang, L. J. McReynolds, C. Shelburne, J. Hu-Li, T. F. Huff, and W. E. Paul. 1997. Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells. Exp. Hematol. 25:357–362.
   PubMedGoogle Scholar
• Sallmyr, A., J. Fan, K. Datta, K. T. Kim, D. Grosu, P. Shapiro, D. Small, and F. Rassool. 2008. Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML. Blood 111:3173–3182.
   PubMed Web of Science ®Google Scholar
• Scheller, M., J. Huelsken, F. Rosenbauer, M. M. Taketo, W. Birchmeier, D. G. Tenen, and A. Leutz. 2006. Hematopoietic stem cell and multilineage defects generated by constitutive beta-catenin activation. Nat. Immunol. 7:1037–1047.
   PubMed Web of Science ®Google Scholar
• Schepers, H., D. van Gosliga, A. T. Wierenga, B. J. Eggen, J. J. Schuringa, and E. Vellenga. 2007. STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells. Blood 110:2880–2888.
   PubMed Web of Science ®Google Scholar
• Schepers, H., A. T. Wierenga, D. van Gosliga, B. J. Eggen, E. Vellenga, and J. J. Schuringa. 2007. Reintroduction of C/EBPα in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis. Blood 110:1317–1325.
   PubMedGoogle Scholar
• Scherr, M., A. Chaturvedi, K. Battmer, I. Dallmann, B. Schultheis, A. Ganser, and M. Eder. 2006. Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 107:3279–3287.
   PubMedGoogle Scholar
• Schindler, C., and J. E. Darnell, Jr. 1995. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Annu. Rev. Biochem. 64:621–651.
   PubMed Web of Science ®Google Scholar
• Schuringa, J. J., K. Y. Chung, G. Morrone, and M. A. Moore. 2004. Constitutive activation of STAT5A promotes human hematopoietic stem cell self-renewal and erythroid differentiation. J. Exp. Med. 200:623–635.
   PubMedGoogle Scholar
• Schuringa, J. J., K. Wu, G. Morrone, and M. A. Moore. 2004. Enforced activation of STAT5A facilitates the generation of embryonic stem-derived hematopoietic stem cells that contribute to hematopoiesis in vivo. Stem Cells 22:1191–1204.
   PubMedGoogle Scholar
• Schwaller, J., E. Parganas, D. Wang, D. Cain, J. C. Aster, I. R. Williams, C. K. Lee, R. Gerthner, T. Kitamura, J. Frantsve, E. Anastasiadou, M. L. Loh, D. E. Levy, J. N. Ihle, and D. G. Gilliland. 2000. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol. Cell 6:693–704.
   PubMed Web of Science ®Google Scholar
• Sexl, V., R. Piekorz, R. Moriggl, J. Rohrer, M. P. Brown, K. D. Bunting, K. Rothammer, M. F. Roussel, and J. N. Ihle. 2000. Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5. Blood 96:2277–2283.
   PubMed Web of Science ®Google Scholar
• Shuai, K., J. Halpern, J. ten Hoeve, X. Rao, and C. L. Sawyers. 1996. Constitutive activation of STAT5 by the BCR-ABL oncogene in chronic myelogenous leukemia. Oncogene 13:247–254.
   PubMed Web of Science ®Google Scholar
• Snow, J. W., N. Abraham, M. C. Ma, N. W. Abbey, B. Herndier, and M. A. Goldsmith. 2002. STAT5 promotes multilineage hematolymphoid development in vivo through effects on early hematopoietic progenitor cells. Blood 99:95–101.
   PubMedGoogle Scholar
• Snow, J. W., N. Abraham, M. C. Ma, S. K. Bronson, and M. A. Goldsmith. 2003. Transgenic bcl-2 is not sufficient to rescue all hematolymphoid defects in STAT5A/5B-deficient mice. Exp. Hematol. 31:1253–1258.
   PubMedGoogle Scholar
• Snow, J. W., N. Abraham, M. C. Ma, and M. A. Goldsmith. 2003. Bone marrow transplant completely rescues hematolymphoid defects in STAT5A/5B-deficient mice. Exp. Hematol. 31:1247–1252.
   PubMedGoogle Scholar
• Socolovsky, M., A. E. Fallon, S. Wang, C. Brugnara, and H. F. Lodish. 1999. Fetal anemia and apoptosis of red cell progenitors in Stat5a−/−5b−/− mice: a direct role for Stat5 in Bcl-X(L) induction. Cell 98:181–191.
   PubMed Web of Science ®Google Scholar
• Socolovsky, M., H. Nam, M. D. Fleming, V. H. Haase, C. Brugnara, and H. F. Lodish. 2001. Ineffective erythropoiesis in Stat5a−/−5b−/− mice due to decreased survival of early erythroblasts. Blood 98:3261–3273.
   PubMed Web of Science ®Google Scholar
• Spiekermann, K., M. Pau, R. Schwab, K. Schmieja, S. Franzrahe, and W. Hiddemann. 2002. Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cells. Exp. Hematol. 30:262–271.
   PubMedGoogle Scholar
• Suzuki, T., and S. Chiba. 2005. Notch signaling in hematopoietic stem cells. Int. J. Hematol. 82:285–294.
   PubMedGoogle Scholar
• van Lohuizen, M., S. Verbeek, P. Krimpenfort, J. Domen, C. Saris, T. Radaszkiewicz, and A. Berns. 1989. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell 56:673–682.
   PubMed Web of Science ®Google Scholar
• Wernig, G., T. Mercher, R. Okabe, R. L. Levine, B. H. Lee, and D. G. Gilliland. 2006. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 107:4274–4281.
   PubMed Web of Science ®Google Scholar
• Wierenga, A. T., H. Schepers, M. A. Moore, E. Vellenga, and J. J. Schuringa. 2006. STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic stem/progenitor cells involves down-modulation of C/EBPα. Blood 107:4326–4333.
   PubMed Web of Science ®Google Scholar
• Ye, D., N. Wolff, L. Li, S. Zhang, and R. L. Ilaria, Jr. 2006. STAT5 signaling is required for the efficient induction and maintenance of CML in mice. Blood 107:4917–4925.
   PubMedGoogle Scholar
• Youn, B. S., C. Mantel, and H. E. Broxmeyer. 2000. Chemokines, chemokine receptors and hematopoiesis. Immunol. Rev. 177:150–174.
   PubMed Web of Science ®Google Scholar
• Zaleskas, V. M., D. S. Krause, K. Lazarides, N. Patel, Y. Hu, S. Li, and R. A. Van Etten. 2006. Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F. PLoS One 1:e18.
   PubMed Web of Science ®Google Scholar
• Zhang, P., J. Iwasaki-Arai, H. Iwasaki, M. L. Fenyus, T. Dayaram, B. M. Owens, H. Shigematsu, E. Levantini, C. S. Huettner, J. A. Lekstrom-Himes, K. Akashi, and D. G. Tenen. 2004. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity 21:853–863.
   PubMedGoogle Scholar
• Zhang, S., S. Fukuda, Y. Lee, G. Hangoc, S. Cooper, R. Spolski, W. J. Leonard, and H. E. Broxmeyer. 2000. Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J. Exp. Med. 192:719–728.
   PubMed Web of Science ®Google Scholar
• Zhu, B. M., S. K. McLaughlin, R. Na, J. Liu, Y. Cui, C. Martin, A. Kimura, G. W. Robinson, N. C. Andrews, and L. Hennighausen. 2008. Hematopoietic-specific Stat5-null mice display microcytic hypochromic anemia associated with reduced transferrin receptor gene expression. Blood 112:2071–2080.
   PubMedGoogle Scholar
• Zippo, A., A. De Robertis, R. Serafini, and S. Oliviero. 2007. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for Myc-dependent transcriptional activation and oncogenic transformation. Nat. Cell Biol. 9:932–944.
   PubMed Web of Science ®Google Scholar