Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Overview

Journal Turk J Haematol

Specialty Hematology

Date 2014 Jan 4

PMID 24385720

Citations 3

Authors

Muge Sayitoglu

Yucel Erbilgin

Ozden Hatirnaz Ng

Inci Yildiz

Tiraje Celkan

Sema Anak

Omer Devecioglu

Gonul Aydogan

Serap Karaman

Nazan Sarper

Cetin Timur

Umit Ure

Ugur Ozbek

Affiliations

Soon will be listed here.

Abstract

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations andabnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALLthis study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, andCALM-AF10) in pediatric T-ALL patients Material and Methods: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured usingquantitative real-time PCR in 43 pediatric T-ALL patients.

Results: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL.Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development(LYL1 and LMO2) were highly expressed during the cortical and mature stages of T-cell development. Furthermore,upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinalinvolvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALLpatient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogeneexpression.

Conclusion: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the needfor extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship totreatment outcome.

Conflict Of Interest: None declared.

Citing Articles

The Role of TAL1 in Hematopoiesis and Leukemogenesis.

Vagapova E, Spirin P, Lebedev T, Prassolov V Acta Naturae. 2018; 10(1):15-23.

PMID: 29713515 PMC: 5916730.

Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish.

Moore F, Garcia E, Lobbardi R, Jain E, Tang Q, Moore J J Exp Med. 2016; 213(6):979-92.

PMID: 27139488 PMC: 4886368. DOI: 10.1084/jem.20152013.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

Ng O, Erbilgin Y, Firtina S, Celkan T, Karakas Z, Aydogan G Blood Cancer J. 2014; 4:e192.

PMID: 24632884 PMC: 3972698. DOI: 10.1038/bcj.2014.12.

References

Erbilgin Y, Sayitoglu M, Hatirnaz O, Dogru O, Akcay A, Tuysuz G . Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL. Dis Markers. 2010; 28(6):353-60. PMC: 3833232. DOI: 10.3233/DMA-2010-0715. View

Weng A, Ferrando A, Lee W, Morris 4th J, Silverman L, Sanchez-Irizarry C . Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004; 306(5694):269-71. DOI: 10.1126/science.1102160. View

Cleary M, Mellentin J, Spies J, Smith S . Chromosomal translocation involving the beta T cell receptor gene in acute leukemia. J Exp Med. 1988; 167(2):682-7. PMC: 2188866. DOI: 10.1084/jem.167.2.682. View

Meijerink J . Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia. Best Pract Res Clin Haematol. 2010; 23(3):307-18. DOI: 10.1016/j.beha.2010.08.002. View

Ferrando A, Look A . Gene expression profiling in T-cell acute lymphoblastic leukemia. Semin Hematol. 2003; 40(4):274-80. DOI: 10.1016/s0037-1963(03)00195-1. View

Hatano M, Roberts C, Minden M, Crist W, Korsmeyer S . Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science. 1991; 253(5015):79-82. DOI: 10.1126/science.1676542. View

Pfaffl M . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001; 29(9):e45. PMC: 55695. DOI: 10.1093/nar/29.9.e45. View

Gottardo N, Jacoby P, Sather H, Reaman G, Baker D, Kees U . Significance of HOX11L2/TLX3 expression in children with T-cell acute lymphoblastic leukemia treated on Children's Cancer Group protocols. Leukemia. 2005; 19(9):1705-8. DOI: 10.1038/sj.leu.2403834. View

Ferrando A, Neuberg D, Dodge R, Paietta E, Larson R, Wiernik P . Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet. 2004; 363(9408):535-6. DOI: 10.1016/S0140-6736(04)15542-6. View

10.

Uckun F, Gaynon P, Sensel M, Nachman J, Trigg M, Steinherz P . Clinical features and treatment outcome of childhood T-lineage acute lymphoblastic leukemia according to the apparent maturational stage of T-lineage leukemic blasts: a Children's Cancer Group study. J Clin Oncol. 1997; 15(6):2214-21. DOI: 10.1200/JCO.1997.15.6.2214. View

11.

Homminga I, Pieters R, Langerak A, de Rooi J, Stubbs A, Verstegen M . Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia. Cancer Cell. 2011; 19(4):484-97. DOI: 10.1016/j.ccr.2011.02.008. View

12.

Pui C, Relling M, Downing J . Acute lymphoblastic leukemia. N Engl J Med. 2004; 350(15):1535-48. DOI: 10.1056/NEJMra023001. View

13.

Malyukova A, Dohda T, von der Lehr N, Akhoondi S, Akhondi S, Corcoran M . The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res. 2007; 67(12):5611-6. DOI: 10.1158/0008-5472.CAN-06-4381. View

14.

Dik W, Pike-Overzet K, Weerkamp F, de Ridder D, de Haas E, Baert M . New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med. 2005; 201(11):1715-23. PMC: 2213269. DOI: 10.1084/jem.20042524. View

15.

De Keersmaecker K, Ferrando A . TLX1-induced T-cell acute lymphoblastic leukemia. Clin Cancer Res. 2011; 17(20):6381-6. DOI: 10.1158/1078-0432.CCR-10-3037. View

16.

Lilleyman J, Hann I, Stevens R, Eden O, Richards S . French American British (FAB) morphological classification of childhood lymphoblastic leukaemia and its clinical importance. J Clin Pathol. 1986; 39(9):998-1002. PMC: 500200. DOI: 10.1136/jcp.39.9.998. View

17.

Grabher C, von Boehmer H, Look A . Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2006; 6(5):347-59. DOI: 10.1038/nrc1880. View

18.

Dik W, Brahim W, Braun C, Asnafi V, Dastugue N, Bernard O . CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes. Leukemia. 2005; 19(11):1948-57. DOI: 10.1038/sj.leu.2403891. View

19.

van Grotel M, Meijerink J, Beverloo H, Langerak A, Buys-Gladdines J, Schneider P . 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(9):1212-21. View

20.

Bach I . The LIM domain: regulation by association. Mech Dev. 2000; 91(1-2):5-17. DOI: 10.1016/s0925-4773(99)00314-7. View