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Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. AIM OF THE WORK: The aim of this work was to study th...

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Autores principales: Hagag, Adel A, Badraia, Ibrahim M, Hassan, Samir M, Abd El-Lateef, Amal E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Università Cattolica del Sacro Cuore 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696468/
https://www.ncbi.nlm.nih.gov/pubmed/26740869
http://dx.doi.org/10.4084/MJHID.2016.008
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author Hagag, Adel A
Badraia, Ibrahim M
Hassan, Samir M
Abd El-Lateef, Amal E
author_facet Hagag, Adel A
Badraia, Ibrahim M
Hassan, Samir M
Abd El-Lateef, Amal E
author_sort Hagag, Adel A
collection PubMed
description BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. AIM OF THE WORK: The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. PATIENTS AND METHODS: This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of WT-1 Gene by real-time PCR in BM samples at time of diagnosis. RESULTS: Positive WT-1 gene expression was found in 22 cases (55%) and negative expression in 18 cases (45%). Positive WT-1 gene expression group (n=22) includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18) includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and the number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were a significantly higher relapse and death rate and a lower rate of CR, DFS, and OAS in negative WT-1 gene expression group. MRD at end of induction therapy was found in 14 cases out of 40 patients. There were significantly higher number of patients with MRD+ in negative WT-1 gene expression group (After the therapy 20 out of 22 (89%) patients with positive WT-1 gene expression attained a negative MRD, while only 6 out of 18 (33%) with negative WT-1 attained a negative MRD) (p-value = 0.006). CONCLUSIONS AND RECOMMENDATION: WT-1 gene expression is an important prognostic factor in patients with ALL, being able to prognosticate a negative MRD. Therefore, we can recommend its incorporation into novel risk-adapted therapeutic strategies in patients with ALL.
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spelling pubmed-46964682016-01-06 Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia Hagag, Adel A Badraia, Ibrahim M Hassan, Samir M Abd El-Lateef, Amal E Mediterr J Hematol Infect Dis Original Article BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. AIM OF THE WORK: The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. PATIENTS AND METHODS: This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of WT-1 Gene by real-time PCR in BM samples at time of diagnosis. RESULTS: Positive WT-1 gene expression was found in 22 cases (55%) and negative expression in 18 cases (45%). Positive WT-1 gene expression group (n=22) includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18) includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and the number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were a significantly higher relapse and death rate and a lower rate of CR, DFS, and OAS in negative WT-1 gene expression group. MRD at end of induction therapy was found in 14 cases out of 40 patients. There were significantly higher number of patients with MRD+ in negative WT-1 gene expression group (After the therapy 20 out of 22 (89%) patients with positive WT-1 gene expression attained a negative MRD, while only 6 out of 18 (33%) with negative WT-1 attained a negative MRD) (p-value = 0.006). CONCLUSIONS AND RECOMMENDATION: WT-1 gene expression is an important prognostic factor in patients with ALL, being able to prognosticate a negative MRD. Therefore, we can recommend its incorporation into novel risk-adapted therapeutic strategies in patients with ALL. Università Cattolica del Sacro Cuore 2016-01-01 /pmc/articles/PMC4696468/ /pubmed/26740869 http://dx.doi.org/10.4084/MJHID.2016.008 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Hagag, Adel A
Badraia, Ibrahim M
Hassan, Samir M
Abd El-Lateef, Amal E
Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title_full Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title_fullStr Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title_full_unstemmed Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title_short Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia
title_sort prognostic impact of wt-1 gene expression in egyptian children with acute lymphoblastic leukemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696468/
https://www.ncbi.nlm.nih.gov/pubmed/26740869
http://dx.doi.org/10.4084/MJHID.2016.008
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