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Gene Review

TLX1  -  T-cell leukemia homeobox 1

Homo sapiens

Synonyms: HOX11, Homeobox protein Hox-11, Proto-oncogene TCL-3, T-cell leukemia homeobox protein 1, T-cell leukemia/lymphoma protein 3, ...
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Disease relevance of TLX1


High impact information on TLX1


Chemical compound and disease context of TLX1


Biological context of TLX1

  • Only the TLX1 oncogene expression subgroup showed difference in leukaemia-specific survival [9].
  • Based on these findings, we identify a synergistic role between TLX1/HOX11 overexpression and Ubr1 inactivation in promoting chromosome missegregation, permitting the accrual of additional chromosome losses and cytogenic abnormalities en route to malignancy.Oncogene (2006) 25, 5752-5763. doi:10.1038/sj.onc.1209573; published online 24 July 2006 [1].
  • Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice [1].
  • Using a whole-genome PCR approach, we show here that TLX1 protein directly interacts with pericentromeric human satellite 2 DNA sequences [10].
  • The interaction was confirmed in vitro and in vivo by gel retardation and chromatin immunoprecipitation assays involving satellite 2 DNA, which contained sequences resembling TLX1 binding sites [10].

Anatomical context of TLX1


Associations of TLX1 with chemical compounds


Physical interactions of TLX1

  • First, a PBX2 Regulatory Element PRE-1048 has been identified which contains a novel DNA-binding sequence and mediates significant activation of the HOX11 gene in K562 cells [14].
  • The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes [2].
  • HOX11 was shown to interact in vitro and in vivo with CTF1 [15].

Regulatory relationships of TLX1

  • The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development [12].
  • The results support the hypothesis that the transforming capacity of HOX11 derives from its ability to alter the expression of genes regulating hematopoietic differentiation and that secondary mutations promoting cell survival or stimulating proliferation are required for progression to malignancy [8].

Other interactions of TLX1

  • Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALLs based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biologic networks with the TLX1- and TLX3-related cases [16].
  • Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed [17].
  • SIL-TAL1 fusion was detected in association with HOX11 expression in one patient and with a t(8;14) (q24;q11) in another [4].
  • The chromosomal translocations involving LMO2 (t(11;14)(p13;q11)), Ttg-1 (t(11;14)(p15;q11)), and Hox11 (t(10;14)(q24;q11)) are among the clearest examples in which it appears that a D or J segment has synapsed with an adventitious heptamer/nonamer at a gene outside of one of the antigen receptor loci [18].
  • Patients with HOX11-positive lymphoblasts have an excellent prognosis when treated with modern combination chemotherapy, while cases at high risk of early failure are included largely in the TAL1- and LYL1-positive groups [19].

Analytical, diagnostic and therapeutic context of TLX1


  1. Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice. Chen, E., Kwon, Y.T., Lim, M.S., Dubé, I.D., Hough, M.R. Oncogene (2006) [Pubmed]
  2. The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Dear, T.N., Sanchez-Garcia, I., Rabbitts, T.H. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study. Asnafi, V., Buzyn, A., Thomas, X., Huguet, F., Vey, N., Boiron, J.M., Reman, O., Cayuela, J.M., Lheritier, V., Vernant, J.P., Fiere, D., Macintyre, E., Dombret, H. Blood (2005) [Pubmed]
  4. HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis. Ballerini, P., Blaise, A., Busson-Le Coniat, M., Su, X.Y., Zucman-Rossi, J., Adam, M., van den Akker, J., Perot, C., Pellegrino, B., Landman-Parker, J., Douay, L., Berger, R., Bernard, O.A. Blood (2002) [Pubmed]
  5. Induction of tolerance to immunogenic tumor antigens associated with lymphomagenesis in HOX11 transgenic mice. Rosic-Kablar, S., Chan, K., Reis, M.D., Dubé, I.D., Hough, M.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint. Kawabe, T., Muslin, A.J., Korsmeyer, S.J. Nature (1997) [Pubmed]
  7. Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Hatano, M., Roberts, C.W., Minden, M., Crist, W.M., Korsmeyer, S.J. Science (1991) [Pubmed]
  8. The HOX11 homeobox-containing gene of human leukemia immortalizes murine hematopoietic precursors. Hawley, R.G., Fong, A.Z., Lu, M., Hawley, T.S. Oncogene (1994) [Pubmed]
  9. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Ferrando, A.A., Neuberg, D.S., Dodge, R.K., Paietta, E., Larson, R.A., Wiernik, P.H., Rowe, J.M., Caligiuri, M.A., Bloomfield, C.D., Look, A.T. Lancet (2004) [Pubmed]
  10. The nuclear oncoprotein TLX1/HOX11 associates with pericentromeric satellite 2 DNA in leukemic T-cells. Heidari, M., Rice, K.L., Phillips, J.K., Kees, U.R., Greene, W.K. Leukemia (2006) [Pubmed]
  11. G1/S transcriptional networks modulated by the HOX11/TLX1 oncogene of T-cell acute lymphoblastic leukemia. Riz, I., Hawley, R.G. Oncogene (2005) [Pubmed]
  12. The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development. Greene, W.K., Bahn, S., Masson, N., Rabbitts, T.H. Mol. Cell. Biol. (1998) [Pubmed]
  13. Tyrosine phosphorylation is required for up-regulation of the HOX-11 (TCL-3) homeobox proto-oncogene in T cells. Zhang, N., Shen, W.F., Ho, A.D., Lu, M. Cancer Res. (1995) [Pubmed]
  14. A complex containing PBX2 contributes to activation of the proto-oncogene HOX11. Brake, R.L., Kees, U.R., Watt, P.M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  15. HOX11 interacts with CTF1 and mediates hematopoietic precursor cell immortalization. Zhang, N., Shen, W., Hawley, R.G., Lu, M. Oncogene (1999) [Pubmed]
  16. HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). Soulier, J., Clappier, E., Cayuela, J.M., Regnault, A., García-Peydró, M., Dombret, H., Baruchel, A., Toribio, M.L., Sigaux, F. Blood (2005) [Pubmed]
  17. 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. Cavé, H., Suciu, S., Preudhomme, C., Poppe, B., Robert, A., Uyttebroeck, A., Malet, M., Boutard, P., Benoit, Y., Mauvieux, L., Lutz, P., Méchinaud, F., Grardel, N., Mazingue, F., Dupont, M., Margueritte, G., Pages, M.P., Bertrand, Y., Plouvier, E., Brunie, G., Bastard, C., Plantaz, D., Vande Velde, I., Hagemeijer, A., Speleman, F., Lessard, M., Otten, J., Vilmer, E., Dastugue, N. Blood (2004) [Pubmed]
  18. Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints. Raghavan, S.C., Kirsch, I.R., Lieber, M.R. J. Biol. Chem. (2001) [Pubmed]
  19. Gene expression profiling in T-cell acute lymphoblastic leukemia. Ferrando, A.A., Look, A.T. Semin. Hematol. (2003) [Pubmed]
  20. Genomic organization of the putative human homeobox proto-oncogene HOX-11 (TCL-3) and its endogenous expression in T cells. Lu, M., Zhang, N., Ho, A.D. Oncogene (1992) [Pubmed]
  21. Joining of recombination signals on the der 14q- chromosome in T-cell acute leukemia with t(10;14) chromosome translocation. Kagan, J., Joe, Y.S., Freireich, E.J. Cancer Res. (1994) [Pubmed]
  22. HOX11 expression in pediatric acute lymphoblastic leukemia is associated with T-cell phenotype. Salvati, P.D., Ranford, P.R., Ford, J., Kees, U.R. Oncogene (1995) [Pubmed]
  23. Detection of translocations involving the HOX11/TCL3-locus in 10q24 by interphase fluorescence in situ hybridization. Kahl, C., Gesk, S., Harder, L., Harbott, J., French, L., Deloukas, P., Grote, W., Schlegelberger, B., Siebert, R. Cancer Genet. Cytogenet. (2001) [Pubmed]
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