| Peer-Reviewed

Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients

Received: 24 May 2014    Accepted: 14 June 2014    Published: 20 July 2014
Views:       Downloads:
Abstract

Objective: The aim of this study was to determine the prognostic value of two structurally related homeobox genes TLX1/HOX11 and TLX3/HOX11L2 on the clinical outcome of T-ALL patients. Material and Methods: The study included 28 newly diagnosed T-ALL patients. HOX11L2 and HOX11 gene expression were detected by real time PCR. Patients received treatment according to the ALL BFM-90 protocol. Results: Of 28 patients, 8(28.6%) expressed HOX11L2 and 4(14.3%) expressed HOX11.The overall survival of patients with HOX11L2 expression was lower than of the patients without HOX11L2 expression (log-rank P<0.025). As regards HOX11 expression, a statistically significant difference in clinical outcome was found, where HOX11 expression conferred a prognostic advantage (p< 0.001). Conclusion: the present study was showed that the outcome of HOX11L2 and HOX11 expression differs, with poor outcome for patients with HOX11l2-expression. Future molecular diagnostics may make use of such leukemia-specific markers as HOX11L2 and HOX11 to detect minimal residual disease.

Published in Journal of Cancer Treatment and Research (Volume 2, Issue 3)
DOI 10.11648/j.jctr.20140203.12
Page(s) 27-32
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

HOX11L2, HOX11, Real Time PCR, T-ALL

References
[1] Chiaretti S., and Foa R.: T-cell Acute lymphoblastic leukemia. Haematologica 2009; 94 (2):160-162.
[2] Thiel E., Kranze B.R., Raghavcher A., Bartran C.R., Loffler H. et al.: Prethymic phenotype and genotype of pre-T (CD7+/ER-) – cell leukemia and its clinical significance within adult acute lymphoblastic leukemia. Blood 1989; 73:1247-1258.
[3] Silverman L.B., Gelber R.D., Dalton V.K., Asselin B.L., Barr R.D. et al.: Improved outcome for children with acute lymphobalstic leukemia: results of Dane-Faber consortium protocol 91-01. Blood 2001; 97, 1211-1218.
[4] Harrison C.T. and Foronil L. : Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Rev Clin Exp Hematol.2002; 3:91-113.
[5] Cauwelier B., Dastugue N., Cools J., Poppe B., Herens C. et al.: Molecular cytogenetics study of 126 unselected T-ALL cases reveals high incidence of Tc beta locus rearrangements and putative new T-cell oncogenes. Leukemia 2006; 20:1238-1244.
[6] Carrol A.J., Crist W.M., Ragab A.H. et al.: The t(1;14)(p34;q11) is nonrandom and restricted to T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1990; 76:1220-4.
[7] Speleman F., Cauwelier B., Dastugue N., Cools J. et al.: A new recurrent inversion, inv(7)(p15q34), leads to transcription al activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia 2005; 19:358-66.
[8] Hatano M., Roberts C.W., Minden M., Crist W.M. et al.: Deregulation of a homeopox gene HOX11 by the t(10;14)in T-cell leukemia. Science 1991; 253: 79-82.
[9] Bernard O.A., Busson-Leconiat M., Ballerini P., Mauchauffe M. 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; 15:1495-504.
[10] Baldus. C.D, Thibaut .J, Goekbuget N., Stroux A., Schlee C., Mossner M., Burmeister T., Schwartz S., Bloomfield C.D., Hoelzer D., Thiel E. and Hofmann W.K.: Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. Haematologica 2009;94:1383-1390
[11] Asnafi V., Radford Weiss L., Dastugue N., Bayle C. et al.: CALM-AFT10 is a common fusion transcript in T-ALL and is specific to the TCR gamma delta lineage. Blood 2003; 102:1000-1006.
[12] Harrisan CJ : Cytogenetics of Pediatric and adolescent acute lymphoblastic leukemias. Br J Haematol 2009; 144(2):147-56.
[13] ChenE, HuangX, ZhengY, Li Y, ChesneyA, Ben-David Y, Yang E, Hough MR: Phosphorylation of HOX11/TLX1 on Threonine-247 during mitosis modulates expression of cyclin B1. Molecular Cancer 2010; 9:246
[14] Sekimizu M, Sunami S, Nakazawa A, Hayashi Y, Okimoto Y, Saito AM, Horibe K, Tsurusawa M, Mori T.:Chromosome abnormalities in advanced stage T-cell lymphoblastic lymphoma of children and adolescents: a report from Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) and review of the literature. Br J Haematol. 2011;154(5):612-7
[15] Bene M.C., Castoldi G., Krapp W., Ludwig W.D. Matutes E. et al.: Proposals for the immunological classification of acute leukemia. European Group for the immunological characteristics of leukemia (EGIL). Leukemia1995; 9:1783-6.
[16] Schrappe M., Reiter A., Ludwig W., Harbott J., Zimmermann M. et al.: Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood 2000; 95(11): 3310-22.
[17] Baldus C.D., Martus P., Burmeister T., Schwartz S., Gokbuget N. et al.: Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J of Clinical Oncology 2007; 25; 24: 3739-3745.
[18] Ballerini P., Blaise A., Busson-Le Coiant M. et al.: HOX11L2 expression defining a clinical subtype of pediatric T-ALL associated with poor prognosis. Blood 2002; 100:991-997.
[19] Martin Val, Grotel J.P.P., Meijerink H., Berna Beverloo et al.: The outcome of molecular- cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia retrospective study of patients treated according to DCOG or COALL protocols. Haematologica 2006 ; 91(9)1212-21
[20] Mauvieux L., Leymarie V., Helias C., Perrusson N. et al. : High incidence of HOX11L2 expression in children with T-ALL. Leukemia 2002; 16(12):2417-22.
[21] Bergeron J., Clappier E., Radford I., Buzyn A., Millien C. et al.: Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-Alls. Blood 2007; 110(7):2324-30.
[22] Dear T.N., Sanchez-Garcia I., Rabbits T.H. : The HOX11 gene encodes a DNA –binding nuclear transcription factor belonging to a distinct family of homeopox genes. Proc Natl Acad USA 1993; 90: 4431-4435.
[23] Kenndy M.A., Gonzalez-Sarmiento R., Kees U.R., Lampert F. et al.: HOX11, a homeopox-containing T-cell oncogene on human chromosome 10q24. Proc Nat Acad Sci USA 1991; 88:8900-04.
[24] Ferrnado A.A., Neuberg D.S., Hams D.O., Staunton J., Loh M.L. et al. : Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002;1:75-87.
[25] Cave H., Suciu S., Preudhomme C., Popper B., Robert 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: Blood 2004; 103:442-50.
[26] Gottardo N.G., Jacoby P.A., Sather H.N., Reaman G.H. et al.: Significance of HOX11L2/TLX3 expression in children with T-cell acute lymphoblastic leukemia treated on children's cancer group protocols. Leukemia 2005; 19:1705-8.
[27] Berger R., Dastugue N., Busson M., Van Den J., Perot C. et al.: t(5;14)/HOX11L2 positive T-cell acute lymphoblastic leukemia. A collaborative study of the group Francais de Cytogenetique Hematologique (GFCH). Leukemia 2003; 17:1851-7.
[28] Ferrnado A.A., Neuberg D.S., Dodge R.K., Paietta E. et al.: Prognostic significance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukemia.. Lancet 2004; 363: 535-6.
[29] Ludwig W.D., Harbott J., Bartram C.R., Komische B., Sperling C. et al.: Incidence and prognostic significance of immunophenotyping subgroups in childhood acute lymphoblastic leukemia.: Experience of the BFM study 86. Recent Results Cancer Res 1993; 131:269-82.
[30] Pullen J., Shuster J.J., Link M., Borowitz M., Amylon M. 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: 1696-707.
[31] Asnafi V., Beljord K., Libura M., Villarese P., Millien C. et al.: Age related phenotypic and oncogeneic differences in T-cell acute lymphoblastic leukemia may reflect thymic atrophy. Blood 2004; 104: 4173-80.
[32] Ballerini P., Landman-Parker J., Cayuela J., Asnafi V., Labopin P. et al.: Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica 2008; 93(11):1658-65.
Cite This Article
  • APA Style

    Said H. Abdu, Doaa Shahin, Mohamed R. El-Shanshory, Hoda A. Salem, Eman A. Amer, et al. (2014). Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients. Journal of Cancer Treatment and Research, 2(3), 27-32. https://doi.org/10.11648/j.jctr.20140203.12

    Copy | Download

    ACS Style

    Said H. Abdu; Doaa Shahin; Mohamed R. El-Shanshory; Hoda A. Salem; Eman A. Amer, et al. Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients. J. Cancer Treat. Res. 2014, 2(3), 27-32. doi: 10.11648/j.jctr.20140203.12

    Copy | Download

    AMA Style

    Said H. Abdu, Doaa Shahin, Mohamed R. El-Shanshory, Hoda A. Salem, Eman A. Amer, et al. Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients. J Cancer Treat Res. 2014;2(3):27-32. doi: 10.11648/j.jctr.20140203.12

    Copy | Download

  • @article{10.11648/j.jctr.20140203.12,
      author = {Said H. Abdu and Doaa Shahin and Mohamed R. El-Shanshory and Hoda A. Salem and Eman A. Amer and Mohamed M. El-Shebeiny},
      title = {Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients},
      journal = {Journal of Cancer Treatment and Research},
      volume = {2},
      number = {3},
      pages = {27-32},
      doi = {10.11648/j.jctr.20140203.12},
      url = {https://doi.org/10.11648/j.jctr.20140203.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20140203.12},
      abstract = {Objective: The aim of this study was to determine the prognostic value of two structurally related homeobox genes TLX1/HOX11 and TLX3/HOX11L2 on the clinical outcome of T-ALL patients. Material and Methods: The study included 28 newly diagnosed T-ALL patients. HOX11L2 and HOX11 gene expression were detected by real time PCR. Patients received treatment according to the ALL BFM-90 protocol. Results: Of 28 patients, 8(28.6%) expressed HOX11L2 and 4(14.3%) expressed HOX11.The overall survival of patients with HOX11L2 expression was lower than of the patients without HOX11L2 expression (log-rank P<0.025).  As regards HOX11 expression, a statistically significant difference in clinical outcome was found, where HOX11 expression conferred a prognostic advantage (p< 0.001). Conclusion: the present study was showed that the outcome of HOX11L2 and HOX11 expression differs, with poor outcome for patients with HOX11l2-expression. Future molecular diagnostics may make use of such leukemia-specific markers as HOX11L2 and HOX11 to detect minimal residual disease.},
     year = {2014}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients
    AU  - Said H. Abdu
    AU  - Doaa Shahin
    AU  - Mohamed R. El-Shanshory
    AU  - Hoda A. Salem
    AU  - Eman A. Amer
    AU  - Mohamed M. El-Shebeiny
    Y1  - 2014/07/20
    PY  - 2014
    N1  - https://doi.org/10.11648/j.jctr.20140203.12
    DO  - 10.11648/j.jctr.20140203.12
    T2  - Journal of Cancer Treatment and Research
    JF  - Journal of Cancer Treatment and Research
    JO  - Journal of Cancer Treatment and Research
    SP  - 27
    EP  - 32
    PB  - Science Publishing Group
    SN  - 2376-7790
    UR  - https://doi.org/10.11648/j.jctr.20140203.12
    AB  - Objective: The aim of this study was to determine the prognostic value of two structurally related homeobox genes TLX1/HOX11 and TLX3/HOX11L2 on the clinical outcome of T-ALL patients. Material and Methods: The study included 28 newly diagnosed T-ALL patients. HOX11L2 and HOX11 gene expression were detected by real time PCR. Patients received treatment according to the ALL BFM-90 protocol. Results: Of 28 patients, 8(28.6%) expressed HOX11L2 and 4(14.3%) expressed HOX11.The overall survival of patients with HOX11L2 expression was lower than of the patients without HOX11L2 expression (log-rank P<0.025).  As regards HOX11 expression, a statistically significant difference in clinical outcome was found, where HOX11 expression conferred a prognostic advantage (p< 0.001). Conclusion: the present study was showed that the outcome of HOX11L2 and HOX11 expression differs, with poor outcome for patients with HOX11l2-expression. Future molecular diagnostics may make use of such leukemia-specific markers as HOX11L2 and HOX11 to detect minimal residual disease.
    VL  - 2
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

  • Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

  • Department of Pediatric, Faculty of Medicine, Tanta University, Tanta, Egypt

  • Department of Clinical Pharmacy, Faculty of pharmacy, Misr University for Science and Technology, Cairo, Egypt

  • Biochemistry Department, Faculty of pharmacy, Modern Science and Art University, Cairo, Egypt

  • Department of Clinical Oncology, Faculty of Medicine, Tanta University, Tanta, Egypt

  • Sections