New insight into hedgehog signaling in hematological malignancies

References

• Nüsslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature 1980;287:795–801.
   PubMed Web of Science ®Google Scholar
• McMahon AP, Ingham PW, Tabin CJ. Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol 2003;53:1–114.
   PubMed Web of Science ®Google Scholar
• Ingham PW, Placzek M. Orchestrating ontogenesis: variations on a theme by sonic hedgehog. Nat Rev Genet 2006;7:841–850.
   PubMed Web of Science ®Google Scholar
• Johnson RL, Scott MP. New players and puzzles in the Hedgehog signaling pathway. Curr Opin Genet Dev 1998;8:450–456.
   PubMed Web of Science ®Google Scholar
• Murone M, Rosenthal A, de Sauvage FJ. Hedgehog signal transduction: from flies to vertebrates. Exp Cell Res 1999;253:25–33.
   PubMed Web of Science ®Google Scholar
• Pasca di Magliano M, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer 2003;3:903–911.
   PubMed Web of Science ®Google Scholar
• Duman-Scheel M, Weng L, Xin S, et al. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature 2002;417:299–304.
   PubMed Web of Science ®Google Scholar
• Dierks C, Grbic J, Zirlik K, et al. Essential role of stromally induced hedgehog signaling in B-cell malignancies. Nat Med 2007;13: 944–951.
   PubMed Web of Science ®Google Scholar
• Eichberger T, Sander V, Schnidar H, et al. Overlapping and distinct transcriptional regulator properties of the GLI1 and GLI2 oncogenes. Genomics 2006;87:616–632.
   PubMed Web of Science ®Google Scholar
• Wang B, Fallon JF, Beachy PA. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell 2000;100:423–434.
   PubMed Web of Science ®Google Scholar
• Geissler K, Zach O. Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway. Ann Hematol 2012;91:645–669.
   Google Scholar
• Aberger F, Kern D, Greil R, et al. Canonical and noncanonical Hedgehog/GLI signaling in hematological malignancies. Vitam Horm 2012;88:25–54.
   PubMed Web of Science ®Google Scholar
• Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med 2004;6:530–539.
   PubMed Web of Science ®Google Scholar
• Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 2008;8:743–754.
   PubMed Web of Science ®Google Scholar
• Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov 2006;5:1026–1033.
   PubMed Web of Science ®Google Scholar
• Hutchin ME, Kariapper MS, Grachtchouk M, et al. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev 2005;19:214–223.
   PubMed Web of Science ®Google Scholar
• Varnat F, Duquet A, Malerba M, et al. Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med 2009;1:338–351.
   PubMed Web of Science ®Google Scholar
• Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med 2009;361:2094–2096.
   PubMed Web of Science ®Google Scholar
• Yoshikawa R, Nakano Y, Tao L, et al. Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy. Br J Cancer 2008;98:1670–1674.
   PubMed Web of Science ®Google Scholar
• Merchant A, Joseph G, Wang Q, et al. Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors. Blood 2010;115:2391–2396.
   PubMed Web of Science ®Google Scholar
• Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004; 431:707–712.
   PubMed Web of Science ®Google Scholar
• Liao X, Siu MK, Au CW, et al. Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 2009;30:131–140.
   PubMed Web of Science ®Google Scholar
• Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003;422:313–317.
   PubMed Web of Science ®Google Scholar
• Anton Aparicio LM, Garcia Campelo R, Cassinello Espinosa J, et al. Prostate cancer and Hedgehog signalling pathway. Clin Transl Oncol 2007;9:420–428.
   PubMed Web of Science ®Google Scholar
• Hegde GV, Munger CM, Emanuel K, et al. Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma. Mol Cancer Ther 2008;7:1450–1460.
   PubMed Web of Science ®Google Scholar
• Lauth M, Toftgard R. Non-canonical activation of GLI transcription factors: implications for targeted anti-cancer therapy. Cell Cycle 2007;6:2458–2463.
   PubMed Web of Science ®Google Scholar
• Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature 2001;411:349–354.
   PubMed Web of Science ®Google Scholar
• Ruiz i Altaba A, Sanchez P, Dahmane N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer 2002;2: 361–372.
   PubMed Web of Science ®Google Scholar
• Xie J, Bartels CM, Barton SW, et al. Targeting hedgehog signaling in cancer: research and clinical developments. Onco Targets Ther 2013;6:1425–1435.
   PubMed Web of Science ®Google Scholar
• Romer JT, Kimura H, Magdaleno S, et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/−)p53(−/−) mice. Cancer Cell 2004;6:229–240.
   PubMed Web of Science ®Google Scholar
• Gu D, Fan Q, Zhang X, Xie J. A role for transcription factor STAT3 signaling in oncogene smoothened-driven carcinogenesis. J Biol Chem 2012;287:38356–38366.
   PubMed Web of Science ®Google Scholar
• Xie J, Aszterbaum M, Zhang X, et al. A role of PDGFRalpha in basal cell carcinoma proliferation. Proc Natl Acad Sci USA 2001;98: 9255–9259.
   PubMed Web of Science ®Google Scholar
• Keysar SB, Le PN, Anderson RT, et al. Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer. Cancer Res 2013;73:3381–3392.
   PubMed Web of Science ®Google Scholar
• Fan Q, He M, Sheng T, et al. Requirement of TGFbeta signaling for SMO-mediated carcinogenesis. J Biol Chem 2010;285:36570–36576.
   Google Scholar
• Hsieh A, Ellsworth R, Hsieh D. Hedgehog/GLI1 regulates IGF dependent malignant behaviors in glioma stem cells. J Cell Physiol 2011;226:1118–1127.
   PubMed Web of Science ®Google Scholar
• Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008;22:2454–2472.
   PubMed Web of Science ®Google Scholar
• Dyer MA, Farrington SM, Mohn D, et al. Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Development 2001;128:1717–1730.
   PubMed Web of Science ®Google Scholar
• Kobune M, Ito Y, Kawano Y, et al. Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-beta2m-/- repopulating cells. Blood 2004;104:1002–1009.
   PubMed Web of Science ®Google Scholar
• Sacedon R, Diez B, Nunez V, et al. Sonic hedgehog is produced by follicular dendritic cells and protects germinal center B cells from apoptosis. J Immunol 2005;174:1456–1461.
   PubMed Web of Science ®Google Scholar
• Drakopoulou E, Outram SV, Rowbotham NJ, et al. Non-redundant role for the transcription factor Gli1 at multiple stages of thymocyte development. Cell Cycle 2010;9:4144–4152.
   PubMed Web of Science ®Google Scholar
• Kappes DJ, He X. CD4-CD8 lineage commitment: an inside view. Nat Immunol 2005;6:761–766.
   PubMed Web of Science ®Google Scholar
• Rowbotham NJ, Hager-Theodorides AL, Cebecauer M, et al. Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation. Blood 2007;109:3757–3766.
   PubMed Web of Science ®Google Scholar
• Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960;25:85–109.
   PubMed Web of Science ®Google Scholar
• Chen Y, Peng C, Li D, et al. Molecular and cellular bases of chronic myeloid leukemia. Protein Cell 2010;1:124–132.
   PubMed Web of Science ®Google Scholar
• Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 1984;63:789–799.
   PubMed Web of Science ®Google Scholar
• Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010;116:3758–3765.
   PubMed Web of Science ®Google Scholar
• Aguayo A, Couban S. State-of-the-art in the management of chronic myelogenous leukemia in the era of the tyrosine kinase inhibitors: evolutionary trends in diagnosis, monitoring and treatment. Leuk Lymphoma 2009;50(Suppl. 2):1–8.
   PubMed Web of Science ®Google Scholar
• Carella AM, Garuti A, Cirmena G, et al. Kinase domain mutations of BCR-ABL identified at diagnosis before imatinib-based therapy are associated with progression in patients with high Sokal risk chronic phase chronic myeloid leukemia. Leuk Lymphoma 2010;51:275–278.
   PubMed Web of Science ®Google Scholar
• Tantiworawit A, Power MM, Barnett MJ, et al. Long-term follow-up of patients with chronic myeloid leukemia in chronic phase developing sudden blast phase on imatinib therapy. Leuk Lymphoma 2012;53:1321–1326.
   PubMed Web of Science ®Google Scholar
• Jagani Z, Dorsch M, Warmuth M. Hedgehog pathway activation in chronic myeloid leukemia. Cell Cycle 2010;9:3449–3456.
   PubMed Web of Science ®Google Scholar
• Dierks C, Beigi R, Guo GR, et al. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell 2008;14:238–249.
   PubMed Web of Science ®Google Scholar
• Liao HF, Su YC, Zheng ZY, et al. Sonic hedgehog signaling regulates Bcr-Abl expression in human chronic myeloid leukemia cells. Biomed Pharmacother 2012;66:378–383.
   PubMed Web of Science ®Google Scholar
• Long B, Zhu H, Zhu C, et al. Activation of the Hedgehog pathway in chronic myelogeneous leukemia patients. J Exp Clin Cancer Res 2011;30:8.
   PubMed Web of Science ®Google Scholar
• Cea M, Cagnetta A, Cirmena G, et al. Tracking molecular relapse of chronic myeloid leukemia by measuring Hedgehog signaling status. Leuk Lymphoma 2013;54:342–352.
   PubMed Web of Science ®Google Scholar
• Zhao C, Chen A, Jamieson CH, et al. Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 2009;458:776–779.
   PubMed Web of Science ®Google Scholar
• Al Baghdadi T, Abonour R, Boswell HS. Novel combination treatments targeting chronic myeloid leukemia stem cells. Clin Lymphoma Myeloma Leuk 2012;12:94–105.
   PubMed Web of Science ®Google Scholar
• Gao J, Graves S, Koch U, et al. Hedgehog signaling is dispensable for adult hematopoietic stem cell function. Cell Stem Cell 2009;4: 548–558.
   PubMed Web of Science ®Google Scholar
• Hofmann I, Stover EH, Cullen DE, et al. Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis. Cell Stem Cell 2009;4:559–567.
   PubMed Web of Science ®Google Scholar
• Lin TL, Wang QH, Brown P, et al. Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926. PLoS One 2010;5:e15262.
   PubMed Web of Science ®Google Scholar
• Ji Z, Mei FC, Johnson BH, et al. Protein kinase A, not Epac, suppresses hedgehog activity and regulates glucocorticoid sensitivity in acute lymphoblastic leukemia cells. J Biol Chem 2007;282: 37370–37377.
   PubMed Web of Science ®Google Scholar
• Warzecha J, Bonke L, Koehl U, et al. The hedgehog inhibitor cyclopamine induces apoptosis in leukemic cells in vitro. Leuk Lymphoma 2008;49:2383–2386.
   PubMed Web of Science ®Google Scholar
• Kawahara T, Kawaguchi-Ihara N, Okuhashi Y, et al. Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Res 2009;29:4629–4632.
   PubMed Web of Science ®Google Scholar
• Bai LY, Weng JR, Lo WJ, et al. Inhibition of hedgehog signaling induces monocytic differentiation of HL-60 cells. Leuk Lymphoma 2012;53:1196–1202.
   PubMed Web of Science ®Google Scholar
• Chang VY, Basso G, Sakamoto KM, Nelson SF. Identification of somatic and germline mutations using whole exome sequencing of congenital acute lymphoblastic leukemia. BMC Cancer 2013; 13:55.
   PubMed Web of Science ®Google Scholar
• Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175–187.
   PubMed Web of Science ®Google Scholar
• Huff CA, Matsui W. Multiple myeloma cancer stem cells. J Clin Oncol 2008;26:2895–2900.
   PubMed Web of Science ®Google Scholar
• Matsui W, Wang Q, Barber JP, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 2008;68:190–197.
   PubMed Web of Science ®Google Scholar
• Matsui W, Huff CA, Wang Q, et al. Characterization of clonogenic multiple myeloma cells. Blood 2004;103:2332–2336.
   PubMed Web of Science ®Google Scholar
• Peacock CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 2007;104:4048–4053.
   PubMed Web of Science ®Google Scholar
• Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med 2005;352:804–815.
   PubMed Web of Science ®Google Scholar
• Nagasawa T. Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol 2006;6: 107–116.
   PubMed Web of Science ®Google Scholar
• Singh RR, Kim JE, Davuluri Y, et al. Hedgehog signaling pathway is activated in diffuse large B-cell lymphoma and contributes to tumor cell survival and proliferation. Leukemia 2010;24:1025–1036.
   PubMed Web of Science ®Google Scholar
• Hegde GV, Peterson KJ, Emanuel K, et al. Hedgehog-induced survival of B-cell chronic lymphocytic leukemia cells in a stromal cell microenvironment: a potential new therapeutic target. Mol Cancer Res 2008;6:1928–1936.
   PubMed Web of Science ®Google Scholar
• Fox MF, Pontier A, Gurbuxani S, et al. Stem cell factor expression in B cell malignancies is influenced by the niche. Leuk Lymphoma 2013;54:2274–2280.
   PubMed Web of Science ®Google Scholar
• Decker S, Zirlik K, Djebatchie L, et al. Trisomy 12 and elevated GLI1 and PTCH1 transcript levels are biomarkers for Hedgehog-inhibitor responsiveness in CLL. Blood 2012;119:997–1007.
   PubMed Web of Science ®Google Scholar
• Desch P, Asslaber D, Kern D, et al. Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells. Oncogene 2010;29:4885–4895.
   PubMed Web of Science ®Google Scholar
• Skarbnik AP, Smith MR. Therapies for mantle cell lymphoma: current challenges and a brighter future. Discov Med 2013;15: 177–187.
   PubMedGoogle Scholar
• Ghielmini M, Zucca E. How I treat mantle cell lymphoma. Blood 2009;114:1469–1476.
   PubMed Web of Science ®Google Scholar
• O’Connor OA. Mantle cell lymphoma: identifying novel molecular targets in growth and survival pathways. Hematology Am Soc Hematol Educ Program 2007:270–276.
   Google Scholar
• Hegde GV, Nordgren TM, Munger CM, et al. Novel therapy for therapy-resistant mantle cell lymphoma: multipronged approach with targeting of hedgehog signaling. Int J Cancer 2012;131:2951–2960.
   PubMed Web of Science ®Google Scholar
• Yoon JW, Gallant M, Lamm ML, et al. Noncanonical regulation of the Hedgehog mediator GLI1 by c-MYC in Burkitt lymphoma. Mol Cancer Res 2013;11:604–615.
   PubMed Web of Science ®Google Scholar
• Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica 2010;102:83–87.
   PubMedGoogle Scholar
• Kuppers R. The biology of Hodgkin's lymphoma. Nat Rev Cancer 2009;9:15–27.
   PubMed Web of Science ®Google Scholar
• Kim JE, Singh RR, Cho-Vega JH, et al. Sonic hedgehog signaling proteins and ATP-binding cassette G2 are aberrantly expressed in diffuse large B-cell lymphoma. Mod Pathol 2009;22:1312–1320.
   PubMed Web of Science ®Google Scholar
• Greaves WO, Kim JE, Singh RR, et al. Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Hum Pathol 2011;42:1643–1652.
   PubMed Web of Science ®Google Scholar
• Hager-Theodorides AL, Dessens JT, Outram SV, et al. The transcription factor Gli3 regulates differentiation of fetal CD4- CD8- double-negative thymocytes. Blood 2005;106:1296–1304.
   PubMed Web of Science ®Google Scholar
• Hager-Theodorides AL, Furmanski AL, Ross SE, et al. The Gli3 transcription factor expressed in the thymus stroma controls thymocyte negative selection via Hedgehog-dependent and -independent mechanisms. J Immunol 2009;183:3023–3032.
   PubMed Web of Science ®Google Scholar
• Singh RR, Kunkalla K, Qu C, et al. ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma. Oncogene 2011;30:4874–4886.
   PubMed Web of Science ®Google Scholar
• Stecca B, Ruiz IAA. Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol 2010;2:84–95.
   PubMed Web of Science ®Google Scholar
• Ramirez E, Singh RR, Kunkalla K, et al. Defining causative factors contributing in the activation of hedgehog signaling in diffuse large B-cell lymphoma. Leuk Res 2012;36:1267–1273.
   PubMed Web of Science ®Google Scholar
• Qu C, Liu Y, Kunkalla K, et al. Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-kappaB activation in diffuse large B-cell lymphoma. Blood 2013;121: 4718–4728.
   PubMed Web of Science ®Google Scholar
• Duyster J, Bai RY, Morris SW. Translocations involving anaplastic lymphoma kinase (ALK). Oncogene 2001;20:5623–5637.
   PubMed Web of Science ®Google Scholar
• Singh RR, Cho-Vega JH, Davuluri Y, et al. Sonic hedgehog signaling pathway is activated in ALK-positive anaplastic large cell lymphoma. Cancer Res 2009;69:2550–2558.
   PubMed Web of Science ®Google Scholar
• Lin TL, Matsui W. Hedgehog pathway as a drug target: Smoothened inhibitors in development. Onco Targets Ther 2012;5:47–58.
   PubMed Web of Science ®Google Scholar
• Beauchamp EM, Uren A. A new era for an ancient drug: arsenic trioxide and Hedgehog signaling. Vitam Horm 2012;88:333–354.
   PubMed Web of Science ®Google Scholar
• Kim J, Lee JJ, Gardner D, Beachy PA. Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Proc Natl Acad Sci USA 2010;107:13432–13437.
   PubMed Web of Science ®Google Scholar