Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

NKL homeobox genes in leukemia

Leukemia volume 26, pages 572–581 (2012)Cite this article

Abstract

NK-like (NKL) homeobox genes code for transcription factors, which can act as key regulators in fundamental cellular processes. NKL genes have been implicated in divergent types of cancer. In this review, we summarize the involvement of NKL genes in cancer and leukemia in particular. NKL genes can act as tumor-suppressor genes and as oncogenes, depending on tissue type. Aberrant expression of NKL genes is especially common in T-cell acute lymphoblastic leukemia (T-ALL). In T-ALL, 8 NKL genes have been reported to be highly expressed in specific T-ALL subgroups, and in ∼30% of cases, high expression is caused by chromosomal rearrangement of 1 of 5 NKL genes. Most of these NKL genes are normally not expressed in T-cell development. We hypothesize that the NKL genes might share a similar downstream effect that promotes leukemogenesis, possibly due to mimicking a NKL gene that has a physiological role in early hematopoietic development, such as HHEX. All eight NKL genes posses a conserved Eh1 repressor motif, which has an important role in regulating downstream targets in hematopoiesis and possibly in leukemogenesis as well. Identification of a potential common leukemogenic NKL downstream pathway will provide a promising subject for future studies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gehring WJ . Master Control Genes in Development and Evolution: The Homeobox Story. 1st edn. Yale University Press: New Haven, 1998.

    Google Scholar 

  2. Garber RL, Kuroiwa A, Gehring WJ . Genomic and cDNA clones of the homeotic locus Antennapedia in Drosophila. EMBO J 1983; 2: 2027–2036.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Scott MP, Weiner AJ, Hazelrigg TI, Polisky BA, Pirrotta V, Scalenghe F et al. The molecular organization of the Antennapedia locus of Drosophila. Cell 1983; 35 (3 Part 2): 763–776.

    CAS  PubMed  Google Scholar 

  4. Qian YQ, Billeter M, Otting G, Muller M, Gehring WJ, Wuthrich K . The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell 1989; 59: 573–580.

    CAS  PubMed  Google Scholar 

  5. Holland PW, Booth HA, Bruford EA . Classification and nomenclature of all human homeobox genes. BMC Biol 2007; 5: 47.

    PubMed  PubMed Central  Google Scholar 

  6. Shah N, Sukumar S . The Hox genes and their roles in oncogenesis. Nat Rev Cancer 2010; 10: 361–371.

    CAS  PubMed  Google Scholar 

  7. McGonigle GJ, Lappin TR, Thompson A . Grappling with the HOX network in hematopoiesis and leukemia. Front Biosci 2008; 13: 4297–4308.

    CAS  PubMed  Google Scholar 

  8. Argiropoulos B, Humphries RK . Hox genes in hematopoiesis and leukemogenesis. Oncogene 2007; 26: 6766–6776.

    CAS  PubMed  Google Scholar 

  9. Abramovich C, Humphries RK . Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol 2005; 12: 210–216.

    CAS  PubMed  Google Scholar 

  10. Abramovich C, Pineault N, Ohta H, Humphries RK . Hox genes: from leukemia to hematopoietic stem cell expansion. Ann NY Acad Sci 2005; 1044: 109–116.

    CAS  PubMed  Google Scholar 

  11. Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR . The pathophysiology of HOX genes and their role in cancer. J Pathol 2005; 205: 154–171.

    CAS  PubMed  Google Scholar 

  12. Kim Y, Nirenberg M . Drosophila NK-homeobox genes. Proc Natl Acad Sci USA 1989; 86: 7716–7720.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Wotton KR, Weierud FK, Juarez-Morales JL, Alvares LE, Dietrich S, Lewis KE . Conservation of gene linkage in dispersed vertebrate NK homeobox clusters. Dev Genes Evol 2009; 219: 481–496.

    CAS  PubMed  Google Scholar 

  14. Wang CC, Brodnicki T, Copeland NG, Jenkins NA, Harvey RP . Conserved linkage of NK-2 homeobox gene pairs Nkx2-2/2-4 and Nkx2-1/2-9 in mammals. Mamm Genome 2000; 11: 466–468.

    CAS  PubMed  Google Scholar 

  15. Kwei KA, Kim YH, Girard L, Kao J, Pacyna-Gengelbach M, Salari K et al. Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer. Oncogene 2008; 27: 3635–3640.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 2007; 450: 893–898.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Harris T, Pan Q, Sironi J, Lutz D, Tian J, Sapkar J et al. Both gene amplification and allelic loss occur at 14q13.3 in lung cancer. Clin Cancer Res 2011; 17: 690–699.

    CAS  PubMed  Google Scholar 

  18. Winslow MM, Dayton TL, Verhaak RG, Kim-Kiselak C, Snyder EL, Feldser DM et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 2011; 473: 101–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Smith R, Owen LA, Trem DJ, Wong JS, Whangbo JS, Golub TR et al. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. Cancer Cell 2006; 9: 405–416.

    CAS  PubMed  Google Scholar 

  20. Jishage M, Fujino T, Yamazaki Y, Kuroda H, Nakamura T . Identification of target genes for EWS/ATF-1 chimeric transcription factor. Oncogene 2003; 22: 41–49.

    CAS  PubMed  Google Scholar 

  21. Mossner M, Hopfer O, Nowak D, Baldus CD, Neumann U, Kmetsch A et al. Detection of differential mitotic cell age in bone marrow CD34(+) cells from patients with myelodysplastic syndrome and acute leukemia by analysis of an epigenetic molecular clock DNA signature. Exp Hematol 2010; 38: 661–665.

    CAS  PubMed  Google Scholar 

  22. Kwabi-Addo B, Chung W, Shen L, Ittmann M, Wheeler T, Jelinek J et al. Age-related DNA methylation changes in normal human prostate tissues. Clin Cancer Res 2007; 13: 3796–3802.

    CAS  PubMed  Google Scholar 

  23. Zhang Y, Rowley JD . Chromatin structural elements and chromosomal translocations in leukemia. DNA Repair (Amst) 2006; 5: 1282–1297.

    CAS  Google Scholar 

  24. Homminga I, Pieters R, Langerak AW, de Rooi JJ, Stubbs A, Verstegen M et al. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia. Cancer Cell 2011; 19: 484–497.

    CAS  PubMed  Google Scholar 

  25. Novershtern N, Subramanian A, Lawton LN, Mak RH, Haining WN, McConkey ME et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell 2011; 144: 296–309.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Asnafi V, Beldjord K, Libura M, Villarese P, Millien C, Ballerini P et al. Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy. Blood 2004; 104: 4173–4180.

    CAS  PubMed  Google Scholar 

  27. van Grotel M, Meijerink JP, van Wering ER, Langerak AW, Beverloo HB, Buijs-Gladdines JG et al. Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences. Leukemia 2008; 22: 124–131.

    CAS  PubMed  Google Scholar 

  28. Ludwig WD, Harbott J, Bartram CR, Komischke B, Sperling C, Teichmann JV et al. Incidence and prognostic significance of immunophenotypic subgroups in childhood acute lymphoblastic leukemia: experience of the BFM study 86. Recent Results Cancer Res 1993; 131: 269–282.

    Article  CAS  PubMed  Google Scholar 

  29. Pullen J, Shuster JJ, Link M, Borowitz M, Amylon M, Carroll AJ et al. Significance of commonly used prognostic factors differs for children with T cell acute lymphocytic leukemia (ALL), as compared to those with B-precursor ALL. A Pediatric Oncology Group (POG) study. Leukemia 1999; 13: 1696–1707.

    CAS  PubMed  Google Scholar 

  30. Ferrando AA, Neuberg DS, Dodge RK, Paietta E, Larson RA, Wiernik PH et al. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet 2004; 363: 535–536.

    CAS  PubMed  Google Scholar 

  31. Ferrando AA, Neuberg DS, Staunton J, Loh ML, Huard C, Raimondi SC et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002; 1: 75–87.

    CAS  PubMed  Google Scholar 

  32. Kees UR, Heerema NA, Kumar R, Watt PM, Baker DL, La MK et al. Expression of HOX11 in childhood T-lineage acute lymphoblastic leukaemia can occur in the absence of cytogenetic aberration at 10q24: a study from the Children's Cancer Group (CCG). Leukemia 2003; 17: 887–893.

    CAS  PubMed  Google Scholar 

  33. Berger R, Dastugue N, Busson M, Van Den Akker J, Perot C, Ballerini P et al. t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Francais de Cytogenetique Hematologique (GFCH). Leukemia 2003; 17: 1851–1857.

    CAS  PubMed  Google Scholar 

  34. Cave H, Suciu S, Preudhomme C, Poppe B, Robert A, Uyttebroeck A et al. Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. Blood 2004; 103: 442–450.

    CAS  PubMed  Google Scholar 

  35. Schneider NR, Carroll AJ, Shuster JJ, Pullen DJ, Link MP, Borowitz MJ et al. New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a pediatric oncology group report of 343 cases. Blood 2000; 96: 2543–2549.

    CAS  PubMed  Google Scholar 

  36. Salvati PD, Ranford PR, Ford J, Kees UR . HOX11 expression in pediatric acute lymphoblastic leukemia is associated with T-cell phenotype. Oncogene 1995; 11: 1333–1338.

    CAS  PubMed  Google Scholar 

  37. Yamamoto H, Hatano M, Iitsuka Y, Mahyar NS, Yamamoto M, Tokuhisa T . Two forms of Hox11 a T cell leukemia oncogene, are expressed in fetal spleen but not in primary lymphocytes. Mol Immunol 1995; 32: 1177–1182.

    CAS  PubMed  Google Scholar 

  38. Kanzler B, Dear TN . Hox11 acts cell autonomously in spleen development and its absence results in altered cell fate of mesenchymal spleen precursors. Dev Biol 2001; 234: 231–243.

    CAS  PubMed  Google Scholar 

  39. Cheng L, Arata A, Mizuguchi R, Qian Y, Karunaratne A, Gray PA et al. Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates. Nat Neurosci 2004; 7: 510–517.

    CAS  PubMed  Google Scholar 

  40. Holland PW, Takahashi T . The evolution of homeobox genes: Implications for the study of brain development. Brain Res Bull 2005; 66: 484–490.

    CAS  PubMed  Google Scholar 

  41. Hawley RG, Fong AZ, Reis MD, Zhang N, Lu M, Hawley TS . Transforming function of the HOX11/TCL3 homeobox gene. Cancer Res 1997; 57: 337–345.

    CAS  PubMed  Google Scholar 

  42. Hough MR, Reis MD, Singaraja R, Bryce DM, Kamel-Reid S, Dardick I et al. A model for spontaneous B-lineage lymphomas in IgHmu-HOX11 transgenic mice. Proc Natl Acad Sci USA 1998; 95: 13853–13858.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Keller G, Wall C, Fong AZ, Hawley TS, Hawley RG . Overexpression of HOX11 leads to the immortalization of embryonic precursors with both primitive and definitive hematopoietic potential. Blood 1998; 92: 877–887.

    CAS  PubMed  Google Scholar 

  44. Hawley RG, Fong AZ, Lu M, Hawley TS . The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors. Oncogene 1994; 9: 1–12.

    CAS  PubMed  Google Scholar 

  45. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V et al. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med 2010; 16: 1321–1327.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Greene WK, Ford J, Dixon D, Tilbrook PA, Watt PM, Klinken SP et al. Enforced expression of HOX11 is associated with an immature phenotype in J2E erythroid cells. Br J Haematol 2002; 118: 909–917.

    CAS  PubMed  Google Scholar 

  47. Riz I, Hawley TS, Johnston H, Hawley RG . Role of TLX1 in T-cell acute lymphoblastic leukaemia pathogenesis. Br J Haematol 2009; 145: 140–143.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Riz I, Akimov SS, Eaker SS, Baxter KK, Lee HJ, Marino-Ramirez L et al. TLX1/HOX11-induced hematopoietic differentiation blockade. Oncogene 2007; 26: 4115–4123.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Dixon DN, Izon DJ, Dagger S, Callow MJ, Taplin RH, Kees UR et al. TLX1/HOX11 transcription factor inhibits differentiation and promotes a non-haemopoietic phenotype in murine bone marrow cells. Br J Haematol 2007; 138: 54–67.

    CAS  PubMed  Google Scholar 

  50. Owens BM, Hawley TS, Spain LM, Kerkel KA, Hawley RG . TLX1/HOX11-mediated disruption of primary thymocyte differentiation prior to the CD4+CD8+ double-positive stage. Br J Haematol 2006; 132: 216–229.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Kawabe T, Muslin AJ, Korsmeyer SJ . HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint. Nature 1997; 385: 454–458.

    CAS  PubMed  Google Scholar 

  52. Riz I, Hawley TS, Luu TV, Lee NH, Hawley RG . TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells. Mol Cancer 2010; 9: 181.

    PubMed  PubMed Central  Google Scholar 

  53. Riz I, Hawley RG . G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia. Oncogene 2005; 24: 5561–5575.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Van Vlierberghe P, van Grotel M, Tchinda J, Lee C, Beverloo HB, van der Spek PJ et al. The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia. Blood 2008; 111: 4668–4680.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Bernard OA, Busson-LeConiat M, Ballerini P, Mauchauffe M, Della Valle V, Monni R et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia 2001; 15: 1495–1504.

    CAS  PubMed  Google Scholar 

  56. Mauvieux L, Leymarie V, Helias C, Perrusson N, Falkenrodt A, Lioure B et al. High incidence of Hox11L2 expression in children with T-ALL. Leukemia 2002; 16: 2417–2422.

    CAS  PubMed  Google Scholar 

  57. van Grotel M, Meijerink JP, Beverloo HB, Langerak AW, Buys-Gladdines JG, Schneider P et al. The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols. Haematologica 2006; 91: 1212–1221.

    PubMed  Google Scholar 

  58. Ballerini P, Blaise A, Busson-Le Coniat M, Su XY, Zucman-Rossi J, Adam M et al. HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis. Blood 2002; 100: 991–997.

    CAS  PubMed  Google Scholar 

  59. Su XY, Busson M, Della Valle V, Ballerini P, Dastugue N, Talmant P et al. Various types of rearrangements target TLX3 locus in T-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer 2004; 41: 243–249.

    CAS  PubMed  Google Scholar 

  60. Hansen-Hagge TE, Schafer M, Kiyoi H, Morris SW, Whitlock JA, Koch P et al. Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11). Leukemia 2002; 16: 2205–2212.

    CAS  PubMed  Google Scholar 

  61. Van Vlierberghe P, Homminga I, Zuurbier L, Gladdines-Buijs J, van Wering ER, Horstmann M et al. Cooperative genetic defects in TLX3 rearranged pediatric T-ALL. Leukemia 2008; 22: 762–770.

    CAS  PubMed  Google Scholar 

  62. Soulier J, Clappier E, Cayuela JM, Regnault A, Garcia-Peydro M, Dombret H et al. HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). Blood 2005; 106: 274–286.

    CAS  PubMed  Google Scholar 

  63. Baak U, Gokbuget N, Orawa H, Schwartz S, Hoelzer D, Thiel E et al. Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group. Leukemia 2008; 22: 1154–1160.

    CAS  PubMed  Google Scholar 

  64. Nagel S, Kaufmann M, Drexler HG, MacLeod RA . The cardiac homeobox gene NKX2-5 is deregulated by juxtaposition with BCL11B in pediatric T-ALL cell lines via a novel t(5;14)(q35.1;q32.2). Cancer Res 2003; 63: 5329–5334.

    CAS  PubMed  Google Scholar 

  65. Przybylski GK, Dik WA, Grabarczyk P, Wanzeck J, Chudobska P, Jankowski K et al. The effect of a novel recombination between the homeobox gene NKX2-5 and the TRD locus in T-cell acute lymphoblastic leukemia on activation of the NKX2-5 gene. Haematologica 2006; 91: 317–321.

    CAS  PubMed  Google Scholar 

  66. Su X, Della-Valle V, Delabesse E, Azgui Z, Berger R, Merle-Beral H et al. Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder. Haematologica 2008; 93: 1081–1085.

    CAS  PubMed  Google Scholar 

  67. Nagel S, Venturini L, Przybylski GK, Grabarczyk P, Meyer C, Kaufmann M et al. NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells. BMC Cancer 2009; 9: 371.

    PubMed  PubMed Central  Google Scholar 

  68. Bellavia D, Campese AF, Alesse E, Vacca A, Felli MP, Balestri A et al. Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice. EMBO J 2000; 19: 3337–3348.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Doucas H, Mann CD, Sutton CD, Garcea G, Neal CP, Berry DP et al. Expression of nuclear Notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated Akt. J Surg Oncol 2008; 97: 63–68.

    PubMed  Google Scholar 

  70. Nagel S, Venturini L, Przybylski GK, Grabarczyk P, Schmidt CA, Meyer C et al. Activation of miR-17-92 by NK-like homeodomain proteins suppresses apoptosis via reduction of E2F1 in T-cell acute lymphoblastic leukemia. Leuk Lymphoma 2009; 50: 101–108.

    CAS  PubMed  Google Scholar 

  71. Nagel S, Meyer C, Quentmeier H, Kaufmann M, Drexler HG, MacLeod RA . MEF2C is activated by multiple mechanisms in a subset of T-acute lymphoblastic leukemia cell lines. Leukemia 2008; 22: 600–607.

    CAS  PubMed  Google Scholar 

  72. Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009; 10: 147–156.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. McCormack MP, Young LF, Vasudevan S, de Graaf CA, Codrington R, Rabbitts TH et al. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 2010; 327: 879–883.

    CAS  PubMed  Google Scholar 

  74. George A, Morse 3rd HC, Justice MJ . The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells. Oncogene 2003; 22: 6764–6773.

    CAS  PubMed  Google Scholar 

  75. Mack DL, Leibowitz DS, Cooper S, Ramsey H, Broxmeyer HE, Hromas R . Down-regulation of the myeloid homeobox protein Hex is essential for normal T-cell development. Immunology 2002; 107: 444–451.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Manfioletti G, Gattei V, Buratti E, Rustighi A, De Iuliis A, Aldinucci D et al. Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells. Blood 1995; 85: 1237–1245.

    CAS  PubMed  Google Scholar 

  77. Jankovic D, Gorello P, Liu T, Ehret S, La Starza R, Desjobert C et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood 2008; 111: 5672–5682.

    CAS  PubMed  Google Scholar 

  78. Borrow J, Shearman AM, Stanton Jr VP, Becher R, Collins T, Williams AJ et al. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996; 12: 159–167.

    CAS  PubMed  Google Scholar 

  79. Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K et al. Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia. Nat Genet 1996; 12: 154–158.

    CAS  PubMed  Google Scholar 

  80. Taketani T, Taki T, Shibuya N, Ito E, Kitazawa J, Terui K et al. The HOXD11 gene is fused to the NUP98 gene in acute myeloid leukemia with t(2;11)(q31;p15). Cancer Res 2002; 62: 33–37.

    CAS  PubMed  Google Scholar 

  81. Panagopoulos I, Isaksson M, Billstrom R, Strombeck B, Mitelman F, Johansson B . Fusion of the NUP98 gene and the homeobox gene HOXC13 in acute myeloid leukemia with t(11;12)(p15;q13). Genes Chromosomes Cancer 2003; 36: 107–112.

    CAS  PubMed  Google Scholar 

  82. Yassin ER, Sarma NJ, Abdul-Nabi AM, Dombrowski J, Han Y, Takeda A et al. Dissection of the transformation of primary human hematopoietic cells by the oncogene NUP98-HOXA9. PloS One 2009; 4: e6719.

    PubMed  PubMed Central  Google Scholar 

  83. Kusy S, Gerby B, Goardon N, Gault N, Ferri F, Gerard D et al. NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia. J Exp Med 2010; 207: 2141–2156.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Herblot S, Steff AM, Hugo P, Aplan PD, Hoang T . SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression. Nat Immunol 2000; 1: 138–144.

    CAS  PubMed  Google Scholar 

  85. Bash RO, Hall S, Timmons CF, Crist WM, Amylon M, Smith RG et al. Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study. Blood 1995; 86: 666–676.

    CAS  PubMed  Google Scholar 

  86. Armstrong SA, Look AT . Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005; 23: 6306–6315.

    CAS  PubMed  Google Scholar 

  87. Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K, McJunkin K et al. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 2010; 12: 372–379.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Korkmaz KS, Korkmaz CG, Ragnhildstveit E, Kizildag S, Pretlow TG, Saatcioglu F . Full-length cDNA sequence and genomic organization of human NKX3A–alternative forms and regulation by both androgens and estrogens. Gene 2000; 260: 25–36.

    CAS  PubMed  Google Scholar 

  89. Deguchi Y, Kehrl JH . Selective expression of two homeobox genes in CD34-positive cells from human bone marrow. Blood 1991; 78: 323–328.

    CAS  PubMed  Google Scholar 

  90. Deguchi Y, Thevenin C, Kehrl JH . Stable expression of HB24, a diverged human homeobox gene, in T lymphocytes induces genes involved in T cell activation and growth. J Biol Chem 1992; 267: 8222–8229.

    CAS  PubMed  Google Scholar 

  91. Deguchi Y, Moroney JF, Wilson GL, Fox CH, Winter HS, Kehrl JH . Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes. New Biol 1991; 3: 353–363.

    CAS  PubMed  Google Scholar 

  92. Deguchi Y, Kehrl JH . High level expression of the homeobox gene HB24 in a human T-cell line confers the ability to form tumors in nude mice. Cancer Res 1993; 53: 373–377.

    CAS  PubMed  Google Scholar 

  93. Deguchi Y, Kirschenbaum A, Kehrl JH . A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia. Blood 1992; 79: 2841–2848.

    CAS  PubMed  Google Scholar 

  94. Jawad M, Seedhouse CH, Russell N, Plumb M . Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia. Blood 2006; 108: 3916–3918.

    CAS  PubMed  Google Scholar 

  95. Rawat VP, Arseni N, Ahmed F, Mulaw MA, Thoene S, Heilmeier B et al. The vent-like homeobox gene VENTX promotes human myeloid differentiation and is highly expressed in acute myeloid leukemia. Proc Natl Acad Sci USA 2010; 107: 16946–16951.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Gao H, Le Y, Wu X, Silberstein LE, Giese RW, Zhu Z . VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription repressor, is a putative tumor suppressor. Cancer Res 2010; 70: 202–211.

    CAS  PubMed  Google Scholar 

  97. Wu X, Gao H, Ke W, Hager M, Xiao S, Freeman MR et al. VentX trans-activates p53 and p16ink4a to regulate cellular senescence. J Biol Chem 2011; 286: 12693–12701.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Ferrari N, Palmisano GL, Paleari L, Basso G, Mangioni M, Fidanza V et al. DLX genes as targets of ALL-1: DLX 2,3,4 down-regulation in t(4;11) acute lymphoblastic leukemias. J Leukoc Biol 2003; 74: 302–305.

    CAS  PubMed  Google Scholar 

  99. Campo Dell’Orto M, Banelli B, Giarin E, Accordi B, Trentin L, Romani M et al. Down-regulation of DLX3 expression in MLL-AF4 childhood lymphoblastic leukemias is mediated by promoter region hypermethylation. Oncology Rep 2007; 18: 417–423.

    Google Scholar 

  100. Stumpel DJ, Schneider P, van Roon EH, Boer JM, de Lorenzo P, Valsecchi MG et al. Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options. Blood 2009; 114: 5490–5498.

    CAS  PubMed  Google Scholar 

  101. Abate-Shen C . Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer 2002; 2: 777–785.

    CAS  PubMed  Google Scholar 

  102. Greene WK, Bahn S, Masson N, Rabbitts TH . The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development. Mol Cell Biol 1998; 18: 7030–7037.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Muhr J, Andersson E, Persson M, Jessell TM, Ericson J . Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube. Cell 2001; 104: 861–873.

    CAS  PubMed  Google Scholar 

  104. Smith ST, Jaynes JB . A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo. Dev (Cambridge, England) 1996; 122: 3141–3150.

    CAS  Google Scholar 

  105. Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP . Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development (Cambridge, England) 1993; 119: 969.

    CAS  Google Scholar 

  106. Desjobert C, Noy P, Swingler T, Williams H, Gaston K, Jayaraman PS . The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors. Biochem J 2009; 417: 121–132.

    CAS  PubMed  Google Scholar 

  107. Chen G, Fernandez J, Mische S, Courey AJ . A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes Dev 1999; 13: 2218–2230.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Choi CY, Kim YH, Kwon HJ, Kim Y . The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription. J Biol Chem 1999; 274: 33194–33197.

    CAS  PubMed  Google Scholar 

  109. Swingler TE, Bess KL, Yao J, Stifani S, Jayaraman PS . The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells. J Biol Chem 2004; 279: 34938–34947.

    CAS  PubMed  Google Scholar 

  110. Rice KL, Kees UR, Greene WK . Transcriptional regulation of FHL1 by TLX1/HOX11 is dosage, cell-type and promoter context-dependent. Biochem Biophys Res Commun 2008; 367: 707–713.

    CAS  PubMed  Google Scholar 

  111. Riz I, Lee HJ, Baxter KK, Behnam R, Hawley TS, Hawley RG . Transcriptional activation by TLX1/HOX11 involves Gro/TLE corepressors. Biochem Biophys Res Commun 2009; 380: 361–365.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Dayyani F, Wang J, Yeh JR, Ahn EY, Tobey E, Zhang DE et al. Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival. Blood 2008; 111: 4338–4347.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Fraga MF, Berdasco M, Ballestar E, Ropero S, Lopez-Nieva P, Lopez-Serra L et al. Epigenetic inactivation of the Groucho homologue gene TLE1 in hematologic malignancies. Cancer Res 2008; 68: 4116–4122.

    CAS  PubMed  Google Scholar 

  114. Liu C, Glasser SW, Wan H, Whitsett JA . GATA-6 and thyroid transcription factor-1 directly interact and regulate surfactant protein-C gene expression. J Biol Chem 2002; 277: 4519–4525.

    CAS  PubMed  Google Scholar 

  115. Nishida W, Nakamura M, Mori S, Takahashi M, Ohkawa Y, Tadokoro S et al. A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes. J Biol Chem 2002; 277: 7308–7317.

    CAS  PubMed  Google Scholar 

  116. Sepulveda JL, Belaguli N, Nigam V, Chen CY, Nemer M, Schwartz RJ . GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: role for regulating early cardiac gene expression. Mol Cell Biol 1998; 18: 3405–3415.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Sepulveda JL, Vlahopoulos S, Iyer D, Belaguli N, Schwartz RJ . Combinatorial expression of GATA4, Nkx2-5, and serum response factor directs early cardiac gene activity. J Biol Chem 2002; 277: 25775–25782.

    CAS  PubMed  Google Scholar 

  118. Weidenfeld J, Shu W, Zhang L, Millar SE, Morrisey EE . The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. J Biol Chem 2002; 277: 21061–21070.

    CAS  PubMed  Google Scholar 

  119. Bellavia D, Campese AF, Checquolo S, Balestri A, Biondi A, Cazzaniga G et al. Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci USA 2002; 99: 3788–3793.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Sellar GC, Li L, Watt KP, Nelkin BD, Rabiasz GJ, Stronach EA et al. BARX2 induces cadherin 6 expression and is a functional suppressor of ovarian cancer progression. Cancer Res 2001; 61: 6977–6981.

    CAS  PubMed  Google Scholar 

  121. Davis M, Hitchcock A, Foulkes WD, Campbell IG . Refinement of two chromosome 11q regions of loss of heterozygosity in ovarian cancer. Cancer Res 1996; 56: 741–744.

    CAS  PubMed  Google Scholar 

  122. Gabra H, Watson JE, Taylor KJ, Mackay J, Leonard RC, Steel CM et al. Definition and refinement of a region of loss of heterozygosity at 11q23.3-q24.3 in epithelial ovarian cancer associated with poor prognosis. Cancer Res 1996; 56: 950–954.

    CAS  PubMed  Google Scholar 

  123. Noonan FC, Mutch DG, Ann Mallon M, Goodfellow PJ . Characterization of the homeodomain gene EMX2: sequence conservation, expression analysis, and a search for mutations in endometrial cancers. Genomics 2001; 76: 37–44.

    CAS  PubMed  Google Scholar 

  124. Wang X, Zbou C, Qiu G, Fan J, Tang H, Peng Z . Screening of new tumor suppressor genes in sporadic colorectal cancer patients. Hepato-Gastroenterology 2008; 55: 2039–2044.

    CAS  PubMed  Google Scholar 

  125. Cavalli LR, Man YG, Schwartz AM, Rone JD, Zhang Y, Urban CA et al. Amplification of the BP1 homeobox gene in breast cancer. Cancer Genet Cytogenet 2008; 187: 19–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Sliwinski T, Synowiec E, Czarny P, Gomulak P, Forma E, Morawiec Z et al. The c.469+46_56del mutation in the homeobox MSX1 gene–a novel risk factor in breast cancer? Cancer Epidemiol 2010; 34: 652–655.

    CAS  PubMed  Google Scholar 

  127. Zheng SL, Ju JH, Chang BL, Ortner E, Sun J, Isaacs SD et al. Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function. Cancer Res 2006; 66: 69–77.

    CAS  PubMed  Google Scholar 

  128. Stevens TA, Meech R . BARX2 and estrogen receptor-alpha (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion. Oncogene 2006; 25: 5426–5435.

    CAS  PubMed  Google Scholar 

  129. Schwartz AM, Man YG, Rezaei MK, Simmens SJ, Berg PE . BP1, a homeoprotein, is significantly expressed in prostate adenocarcinoma and is concordant with prostatic intraepithelial neoplasia. Mod Pathol 2009; 22: 1–6.

    CAS  PubMed  Google Scholar 

  130. Yu M, Wan Y, Zou Q . Prognostic significance of BP1 mRNA expression level in patients with non-small cell lung cancer. Clin Biochem 2008; 41: 824–830.

    CAS  PubMed  Google Scholar 

  131. Awwad RT, Do K, Stevenson H, Fu SW, Lo-Coco F, Costello M et al. Overexpression of BP1, a homeobox gene, is associated with resistance to all-trans retinoic acid in acute promyelocytic leukemia cells. Ann Hematol 2008; 87: 195–203.

    CAS  PubMed  Google Scholar 

  132. Haga SB, Fu S, Karp JE, Ross DD, Williams DM, Hankins WD et al. BP1, a new homeobox gene, is frequently expressed in acute leukemias. Leukemia 2000; 14: 1867–1875.

    CAS  PubMed  Google Scholar 

  133. Fu SW, Schwartz A, Stevenson H, Pinzone JJ, Davenport GJ, Orenstein JM et al. Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer. Breast Cancer Res 2003; 5: R82–R87.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Tan Y, Cheung M, Pei J, Menges CW, Godwin AK, Testa JR . Upregulation of DLX5 promotes ovarian cancer cell proliferation by enhancing IRS-2-AKT signaling. Cancer Res 2010; 70: 9197–9206.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Kato T, Sato N, Takano A, Miyamoto M, Nishimura H, Tsuchiya E et al. Activation of placenta-specific transcription factor distal-less homeobox 5 predicts clinical outcome in primary lung cancer patients. Clin Cancer Res 2008; 14: 2363–2370.

    CAS  PubMed  Google Scholar 

  136. Yu M, Smolen GA, Zhang J, Wittner B, Schott BJ, Brachtel E et al. A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression. Genes Dev 2009; 23: 1737–1742.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Satoh K, Hamada S, Kanno A, Hirota M, Umino J, Ito H et al. Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 2010; 45: 763–770.

    CAS  PubMed  Google Scholar 

  138. Satoh K, Hamada S, Kanno A, Ishida K, Ito H, Hirota M et al. Evaluation of MSX2 mRNA in brush cytology specimens distinguished pancreatic carcinoma from chronic pancreatitis. Cancer Sci 2011; 102: 157–161.

    CAS  PubMed  Google Scholar 

  139. Satoh K, Hamada S, Kimura K, Kanno A, Hirota M, Umino J et al. Up-regulation of MSX2 enhances the malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells. Am J Pathol 2008; 172: 926–939.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Shibata K, Kajiyama H, Yamamoto E, Terauchi M, Ino K, Nawa A et al. Establishment and characterization of an ovarian yolk sac tumor cell line reveals possible involvement of Nkx2.5 in tumor development. Oncology 2008; 74: 104–111.

    CAS  PubMed  Google Scholar 

  141. Turashvili G, Bouchal J, Burkadze G, Kolar Z . Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 2005; 149: 57–62.

    CAS  PubMed  Google Scholar 

  142. Gelmann EP, Bowen C, Bubendorf L . Expression of NKX3.1 in normal and malignant tissues. Prostate 2003; 55: 111–117.

    CAS  PubMed  Google Scholar 

  143. Hollington P, Neufing P, Kalionis B, Waring P, Bentel J, Wattchow D et al. Expression and localization of homeodomain proteins DLX4, HB9 and HB24 in malignant and benign human colorectal tissues. Anticancer Res 2004; 24: 955–962.

    CAS  PubMed  Google Scholar 

  144. Shim C, Zhang W, Rhee CH, Lee JH . Profiling of differentially expressed genes in human primary cervical cancer by complementary DNA expression array. Clin Cancer Res 1998; 4: 3045–3050.

    CAS  PubMed  Google Scholar 

  145. Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH et al. Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol 2009; 22: 261–272.

    CAS  PubMed  Google Scholar 

  146. Furuta J, Nobeyama Y, Umebayashi Y, Otsuka F, Kikuchi K, Ushijima T . Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas. Cancer Res 2006; 66: 6080–6086.

    CAS  PubMed  Google Scholar 

  147. Rauch T, Li H, Wu X, Pfeifer GP . MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. Cancer Res 2006; 66: 7939–7947.

    CAS  PubMed  Google Scholar 

  148. Tong WG, Wierda WG, Lin E, Kuang SQ, Bekele BN, Estrov Z et al. Genome-wide DNA methylation profiling of chronic lymphocytic leukemia allows identification of epigenetically repressed molecular pathways with clinical impact. Epigenetics 2010; 5: 499–508.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Miyamoto K, Fukutomi T, Akashi-Tanaka S, Hasegawa T, Asahara T, Sugimura T et al. Identification of 20 genes aberrantly methylated in human breast cancers. Int J Cancer 2005; 116: 407–414.

    CAS  PubMed  Google Scholar 

  150. Okamoto J, Hirata T, Chen Z, Zhou HM, Mikami I, Li H et al. EMX2 is epigenetically silenced and suppresses growth in human lung cancer. Oncogene 2010; 29: 5969–5975.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Bell A, Bell D, Weber RS, El-Naggar AK . CpG island methylation profiling in human salivary gland adenoid cystic carcinoma. Cancer 2011; 117: 2898–2909.

    CAS  PubMed  Google Scholar 

  152. Jin B, Yao B, Li JL, Fields CR, Delmas AL, Liu C et al. DNMT1 and DNMT3B modulate distinct polycomb-mediated histone modifications in colon cancer. Cancer Res 2009; 69: 7412–7421.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Dunwell TL, Hesson LB, Pavlova T, Zabarovska V, Kashuba V, Catchpoole D et al. Epigenetic analysis of childhood acute lymphoblastic leukemia. Epigenetics 2009; 4: 185–193.

    CAS  PubMed  Google Scholar 

  154. Shames DS, Girard L, Gao B, Sato M, Lewis CM, Shivapurkar N et al. A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med 2006; 3: e486.

    PubMed  PubMed Central  Google Scholar 

  155. Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M, Ushijima T . Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2′-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci 2006; 97: 64–71.

    CAS  PubMed  Google Scholar 

  156. Kuang SQ, Tong WG, Yang H, Lin W, Lee MK, Fang ZH et al. Genome-wide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia. Leukemia 2008; 22: 1529–1538.

    CAS  PubMed  Google Scholar 

  157. Kamalakaran S, Varadan V, Giercksky Russnes HE, Levy D, Kendall J, Janevski A et al. DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables. Mol Oncol 2011; 5: 77–92.

    CAS  PubMed  Google Scholar 

  158. Tellez CS, Shen L, Estecio MR, Jelinek J, Gershenwald JE, Issa JP . CpG island methylation profiling in human melanoma cell lines. Melanoma Res 2009; 19: 146–155.

    CAS  PubMed  Google Scholar 

  159. Asatiani E, Huang WX, Wang A, Rodriguez Ortner E, Cavalli LR, Haddad BR et al. Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer. Cancer Res 2005; 65: 1164–1173.

    CAS  PubMed  Google Scholar 

  160. Lai HC, Lin YW, Huang TH, Yan P, Huang RL, Wang HC et al. Identification of novel DNA methylation markers in cervical cancer. Int J Cancer 2008; 123: 161–167.

    CAS  PubMed  Google Scholar 

  161. Lai HC, Lin YW, Huang RL, Chung MT, Wang HC, Liao YP et al. Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse. Cancer 2010; 116: 4266–4274.

    CAS  PubMed  Google Scholar 

  162. Taylor KH, Pena-Hernandez KE, Davis JW, Arthur GL, Duff DJ, Shi H et al. Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia. Cancer Res 2007; 67: 2617–2625.

    CAS  PubMed  Google Scholar 

  163. Rahmatpanah FB, Carstens S, Guo J, Sjahputera O, Taylor KH, Duff D et al. Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior. Leukemia 2006; 20: 1855–1862.

    CAS  PubMed  Google Scholar 

  164. Wu X, Rauch TA, Zhong X, Bennett WP, Latif F, Krex D et al. CpG island hypermethylation in human astrocytomas. Cancer Res 2010; 70: 2718–2727.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Wang Y, Hayakawa J, Long F, Yu Q, Cho AH, Rondeau G et al. ‘Promoter array’ studies identify cohorts of genes directly regulated by methylation, copy number change, or transcription factor binding in human cancer cells. Ann NY Acad Sci 2005; 1058: 162–185.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands

    I Homminga, R Pieters & J P P Meijerink

Authors
  1. I Homminga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Pieters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J P P Meijerink
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J P P Meijerink.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Homminga, I., Pieters, R. & Meijerink, J. NKL homeobox genes in leukemia. Leukemia 26, 572–581 (2012). https://doi.org/10.1038/leu.2011.330

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.330

Keywords

This article is cited by

Search

Advanced search

Quick links