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

OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogene...

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Main Authors: Müge Sayitoğlu, Yücel Erbilgin, Özden Hatırnaz, İnci Yıldız, Tiraje Celkan, Sema Anak, Ömer Devecioğlu, Gönül Aydoğan, Serap Karaman, Nazan Sarper, Çetin Timur, Ümit Üre, Uğur Özbek
Format: Article
Language:English
Published: Galenos Publishing House 2012-12-01
Series:Turkish Journal of Hematology
Subjects:
Online Access:https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-13540
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author Müge Sayitoğlu
Yücel Erbilgin
Özden Hatırnaz
İnci Yıldız
Tiraje Celkan
Sema Anak
Ömer Devecioğlu
Gönül Aydoğan
Serap Karaman
Nazan Sarper
Çetin Timur
Ümit Üre
Uğur Özbek
author_facet Müge Sayitoğlu
Yücel Erbilgin
Özden Hatırnaz
İnci Yıldız
Tiraje Celkan
Sema Anak
Ömer Devecioğlu
Gönül Aydoğan
Serap Karaman
Nazan Sarper
Çetin Timur
Ümit Üre
Uğur Özbek
author_sort Müge Sayitoğlu
collection DOAJ
description OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, and CALM-AF10) in pediatric T-ALL patients. METHODS: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured using quantitative 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 TLX1 and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10 fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinal involvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALL patient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogene expression. CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the need for extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship to treatment outcome.
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spelling doaj.art-b81ce4f098fd45aea7c8caae301e35cf2023-02-15T16:09:16ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632012-12-0129432533310.5505/tjh.2012.13540TJH-13540Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)Müge Sayitoğlu0Yücel Erbilgin1Özden Hatırnaz2İnci Yıldız3Tiraje Celkan4Sema Anak5Ömer Devecioğlu6Gönül Aydoğan7Serap Karaman8Nazan Sarper9Çetin Timur10Ümit Üre11Uğur Özbek12İstanbul University, Department Of Genetics, Institute Of Experimental Medicine, İstanbul, Turkeyİstanbul University, Department Of Genetics, Institute Of Experimental Medicine, İstanbul, Turkeyİstanbul University, Department Of Genetics, Institute Of Experimental Medicine, İstanbul, Turkeyİstanbul University, Cerrahpaşa School Of Medicine, Department Of Pediatric Hematology, İstanbul, Turkeyİstanbul University, Cerrahpaşa School Of Medicine, Department Of Pediatric Hematology, İstanbul, Turkeyİstanbul University, İstanbul School Of Medicine, Department Of Pediatric Hematology, İstanbul, Turkeyİstanbul University, İstanbul School Of Medicine, Department Of Pediatric Hematology, İstanbul, TurkeyBakırköy Maternity And Children's Hospital, Department Of Pediatrics, İstanbul, TurkeyMinistry Of Health Şişli Etfal Teaching Hospital, Department Of Pediatric Hematology, İstanbul, TurkeyKocaeli School Of Medicine, Department Of Pediatric Hematology, Kocaeli, TurkeyMinistry Of Health Göztepe Teaching Hospital, Department Of Pediatric Hematology, İstanbul, TurkeyMinistry Of Health Bakırköy Sadi Konuk Teaching Hospital, Department Of Hematology, İstanbul, Turkeyİstanbul University, Department Of Genetics, Institute Of Experimental Medicine, İstanbul, TurkeyOBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations and abnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALL this study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, and CALM-AF10) in pediatric T-ALL patients. METHODS: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured using quantitative 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 TLX1 and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10 fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinal involvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALL patient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogene expression. CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the need for extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship to treatment outcome.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-13540t-allpediatrictranscription factorexpressionprognosis
spellingShingle Müge Sayitoğlu
Yücel Erbilgin
Özden Hatırnaz
İnci Yıldız
Tiraje Celkan
Sema Anak
Ömer Devecioğlu
Gönül Aydoğan
Serap Karaman
Nazan Sarper
Çetin Timur
Ümit Üre
Uğur Özbek
Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Turkish Journal of Hematology
t-all
pediatric
transcription factor
expression
prognosis
title Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
title_full Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
title_fullStr Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
title_full_unstemmed Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
title_short Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL)
title_sort upregulation of t cell specific transcription factor expression in pediatric t cell acute lymphoblastic leukemia t all
topic t-all
pediatric
transcription factor
expression
prognosis
url https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-13540
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