HASIB THONDIKODAN, AMITA TREHAN, PRATEEK BHATIA, PARMINDER KAUR, MINU SINGH
{"title":"[摘要]TP53在儿童b细胞急性淋巴细胞白血病中的表达及其与临床病理特征的相关性","authors":"HASIB THONDIKODAN, AMITA TREHAN, PRATEEK BHATIA, PARMINDER KAUR, MINU SINGH","doi":"10.1158/1538-7445.pediatric25-b005","DOIUrl":null,"url":null,"abstract":"Evaluation Of TP53 Expression in Pediatric B- Cell Acute Lymphoblastic Leukemia And Its Correlation With Clinicopathological Profiles Authors: Hasib Tk, Parminder Kaur, Prateek Bhatia, Amita Trehan, Minu SinghAffiliation: Advanced pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh , India. Background: TP53 is a tumor suppressor gene which impacts tumor progression and prognosis in various cancers. TP53 isoforms regulate key processes like cell cycle arrest, apoptosis, and DNA repair. Elevated TP53 expression in B-cell ALL correlates with poor outcomes, making it a potential prognostic marker and therapeutic target. This study aimed at to evaluate the expression of TP53 isoforms and its correlation with clinicopathological profiles in pediatric B-cell ALL patients. Materials and methods: One hundred pediatric B-cell ALL patients (≤12 years) and 20 age matched healthy controls were enrolled for this study. Expression of TP53 full-length and isoform Delta40TP53, Delta133TP53, TP53Beta expressions was checked using qRT-PCR. Fold change was calculated using 2- DDCt method. The expression of isoforms was correlated with various clinical parameters such as risk stratification, blast count, molecular cytogenetics etc. Results: The median age of the patients was 5 years with male: female ratio of 1.2:1. 52% patients had high expression of TP53 full gene expression with the maximum fold change of 9.99-fold. Isoform Delta40TP53, Delta133TP53 and TP53Beta was overexpressed in 17%, 53% and 6% of the patients respectively. Delta133TP53 showed significant association with presence of ETV6::RUNX1 (p=0.047) which is associated with standard risk. The presence of KMT2A::AF4 which is linked with poor prognosis was also associated with TP53Beta expression (p=0.043). However, we could not find significant association between expression of TP53 isoforms and other clinical parameters such as age, gender, TLC, MRD, or progressive disease etc. in pediatric ALL patients. Conclusions: Our study has shown that the expression of full length TP53 and its isoforms is dysregulated in Pediatric B-ALL patients. These findings suggest that Delta133TP53 could be further explored as a potential biomarker for standard risk, whileTP53Beta might serve as an indicator of poor risk in ALL, warranting further investigation in larger cohorts. Citation Format: HASIB THONDIKODAN, AMITA TREHAN, PRATEEK BHATIA, PARMINDER KAUR, MINU SINGH. Evaluation of TP53 expression in pediatric b-cell acute lymphoblastic leukemia and its correlations with clinicopathological profiles [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. 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Background: TP53 is a tumor suppressor gene which impacts tumor progression and prognosis in various cancers. TP53 isoforms regulate key processes like cell cycle arrest, apoptosis, and DNA repair. Elevated TP53 expression in B-cell ALL correlates with poor outcomes, making it a potential prognostic marker and therapeutic target. This study aimed at to evaluate the expression of TP53 isoforms and its correlation with clinicopathological profiles in pediatric B-cell ALL patients. Materials and methods: One hundred pediatric B-cell ALL patients (≤12 years) and 20 age matched healthy controls were enrolled for this study. Expression of TP53 full-length and isoform Delta40TP53, Delta133TP53, TP53Beta expressions was checked using qRT-PCR. Fold change was calculated using 2- DDCt method. The expression of isoforms was correlated with various clinical parameters such as risk stratification, blast count, molecular cytogenetics etc. Results: The median age of the patients was 5 years with male: female ratio of 1.2:1. 52% patients had high expression of TP53 full gene expression with the maximum fold change of 9.99-fold. Isoform Delta40TP53, Delta133TP53 and TP53Beta was overexpressed in 17%, 53% and 6% of the patients respectively. Delta133TP53 showed significant association with presence of ETV6::RUNX1 (p=0.047) which is associated with standard risk. The presence of KMT2A::AF4 which is linked with poor prognosis was also associated with TP53Beta expression (p=0.043). However, we could not find significant association between expression of TP53 isoforms and other clinical parameters such as age, gender, TLC, MRD, or progressive disease etc. in pediatric ALL patients. Conclusions: Our study has shown that the expression of full length TP53 and its isoforms is dysregulated in Pediatric B-ALL patients. These findings suggest that Delta133TP53 could be further explored as a potential biomarker for standard risk, whileTP53Beta might serve as an indicator of poor risk in ALL, warranting further investigation in larger cohorts. Citation Format: HASIB THONDIKODAN, AMITA TREHAN, PRATEEK BHATIA, PARMINDER KAUR, MINU SINGH. Evaluation of TP53 expression in pediatric b-cell acute lymphoblastic leukemia and its correlations with clinicopathological profiles [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. 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引用次数: 0
摘要
TP53在儿童B细胞急性淋巴细胞白血病中的表达及其与临床病理特征的相关性作者:Hasib Tk, Parminder Kaur, Prateek Bhatia, Amita Trehan, Minu singh隶属关系:高级儿科中心,医学教育与研究研究生研究所(PGIMER),昌迪加尔,印度。背景:TP53是一种影响肿瘤进展和预后的抑癌基因。TP53亚型调节细胞周期阻滞、细胞凋亡和DNA修复等关键过程。b细胞ALL中TP53表达升高与预后不良相关,使其成为潜在的预后标志物和治疗靶点。本研究旨在评估儿童b细胞ALL患者TP53亚型的表达及其与临床病理特征的相关性。材料和方法:本研究纳入100例儿童b细胞ALL患者(≤12岁)和20例年龄匹配的健康对照。采用qRT-PCR检测TP53全长及亚型Delta40TP53、Delta133TP53、TP53Beta的表达情况。采用2- DDCt法计算折叠变化。同种异构体的表达与多种临床参数相关,如危险分层、细胞计数、分子细胞遗传学等。结果:患者中位年龄为5岁,男女比例为1.2:1。52%的患者TP53全基因高表达,最大变异倍数为9.99倍。Delta40TP53、Delta133TP53和TP53Beta异构体分别在17%、53%和6%的患者中过表达。Delta133TP53与ETV6::RUNX1存在显著相关(p=0.047),与标准风险相关。与预后不良相关的KMT2A::AF4的存在也与TP53Beta的表达相关(p=0.043)。然而,我们未发现TP53亚型的表达与儿童ALL患者的年龄、性别、TLC、MRD、疾病进展等其他临床参数有显著相关性。结论:我们的研究表明,TP53全长及其亚型在儿童B-ALL患者中表达失调。这些发现表明,Delta133TP53可以进一步作为标准风险的潜在生物标志物,而etp53beta可能作为ALL低风险的指标,值得在更大的队列中进一步研究。引文格式:哈西布·通迪科丹,阿米塔·特雷汉,普拉泰克·巴蒂亚,帕明德·考尔,米努·辛格。TP53在儿童b细胞急性淋巴细胞白血病中的表达及其与临床病理特征的相关性[摘要]。AACR癌症研究特别会议论文集:儿童癌症的发现和创新-从生物学到突破性疗法;2025年9月25日至28日;波士顿,MA。费城(PA): AACR;癌症研究2025;85(18_sup_2): nr B005。
Abstract B005: Evaluation of TP53 expression in pediatric b-cell acute lymphoblastic leukemia and its correlations with clinicopathological profiles
Evaluation Of TP53 Expression in Pediatric B- Cell Acute Lymphoblastic Leukemia And Its Correlation With Clinicopathological Profiles Authors: Hasib Tk, Parminder Kaur, Prateek Bhatia, Amita Trehan, Minu SinghAffiliation: Advanced pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER) , Chandigarh , India. Background: TP53 is a tumor suppressor gene which impacts tumor progression and prognosis in various cancers. TP53 isoforms regulate key processes like cell cycle arrest, apoptosis, and DNA repair. Elevated TP53 expression in B-cell ALL correlates with poor outcomes, making it a potential prognostic marker and therapeutic target. This study aimed at to evaluate the expression of TP53 isoforms and its correlation with clinicopathological profiles in pediatric B-cell ALL patients. Materials and methods: One hundred pediatric B-cell ALL patients (≤12 years) and 20 age matched healthy controls were enrolled for this study. Expression of TP53 full-length and isoform Delta40TP53, Delta133TP53, TP53Beta expressions was checked using qRT-PCR. Fold change was calculated using 2- DDCt method. The expression of isoforms was correlated with various clinical parameters such as risk stratification, blast count, molecular cytogenetics etc. Results: The median age of the patients was 5 years with male: female ratio of 1.2:1. 52% patients had high expression of TP53 full gene expression with the maximum fold change of 9.99-fold. Isoform Delta40TP53, Delta133TP53 and TP53Beta was overexpressed in 17%, 53% and 6% of the patients respectively. Delta133TP53 showed significant association with presence of ETV6::RUNX1 (p=0.047) which is associated with standard risk. The presence of KMT2A::AF4 which is linked with poor prognosis was also associated with TP53Beta expression (p=0.043). However, we could not find significant association between expression of TP53 isoforms and other clinical parameters such as age, gender, TLC, MRD, or progressive disease etc. in pediatric ALL patients. Conclusions: Our study has shown that the expression of full length TP53 and its isoforms is dysregulated in Pediatric B-ALL patients. These findings suggest that Delta133TP53 could be further explored as a potential biomarker for standard risk, whileTP53Beta might serve as an indicator of poor risk in ALL, warranting further investigation in larger cohorts. Citation Format: HASIB THONDIKODAN, AMITA TREHAN, PRATEEK BHATIA, PARMINDER KAUR, MINU SINGH. Evaluation of TP53 expression in pediatric b-cell acute lymphoblastic leukemia and its correlations with clinicopathological profiles [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2): nr B005.
期刊介绍:
Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research.
With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445.
Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.