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Background <p><i>TP53</i> isoforms produced by alternate splicing and promoter usage are shown to play a role in pathogenesis, chemoresistance and relapse in various cancers. Our present study focused on analyzing the expression of different <i>TP53</i> isoforms in pediatric B cell acute lymphoblastic leukemia (B-ALL).</p> Methods <p>We performed the transcriptomic analysis of <i>TP53</i> isoforms expression in publicly available datasets followed by RT-qPCR in our cohort of pediatric B-ALL and correlated with various clinical and hematological parameters.</p> Results <p>Transcriptomic data on B-ALL available online showed overexpression of p53α in B-ALL cases at diagnosis while Δ40p53, p53β and Δ133p53 were downregulated in cases at relapse. In our cohort data (<i>n</i> = 99) at diagnosis, we found the upregulation of the long isoform p53α in 65.65% of patients and the short isoforms Δ133p53 in 61.61% patients and Δ40p53 in 27.27% of the patients, respectively. The over-expression of p53γ and p53β was noted in 19.19% and 14.14% of patients, respectively. To check if <i>TP53</i> gene mutation contributed to this dysregulated isoform expression, we analysed the whole exome data of our B-ALL patients (<i>n</i> = 88). As expected only 3.7% of patients showed mutation in <i>TP53</i> gene. Further, we analysed the correlation with various clinical parameters and found positive association of Δ133p53 with <i>ETV6::RUNX1</i> gene fusion (<i>p</i> = 0.032) which is a known marker of good prognosis in B-ALL. To further validate this observation, we enrolled B-ALL relapse cases (<i>n</i> = 46) where samples at diagnosis were also available (<i>n</i> = 12). Analysis of <i>TP53</i> isoforms expression in relapse B-ALL patients showed significant reduction in the expression of short isoforms of <i>TP53</i> i.e. Δ133p53 (<i>p</i> = 0.0036) and Δ40p53 (<i>p</i> = 0.032).</p> Conclusion <p>Our data show that <i>TP53</i> isoforms are dysregulated in B-ALL at diagnosis as well as at relapse. Short <i>TP53</i> isoforms, particularly Δ133p53 is associated with better prognosis suggesting its potential role in refining risk stratification of B-ALL.</p>

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TP53 isoform dysregulation in pediatric B-ALL: identifying markers of favorable prognosis and relapse-associated dynamic

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Parminder Kaur,
  • T. K. Hasib,
  • Sargeet Kaur,
  • Sharun,
  • Prateek Bhatia,
  • Amita Trehan,
  • Man Updesh Singh Sachdeva,
  • Sreejesh Sreedharanunni,
  • Minu Singh

摘要

Background

TP53 isoforms produced by alternate splicing and promoter usage are shown to play a role in pathogenesis, chemoresistance and relapse in various cancers. Our present study focused on analyzing the expression of different TP53 isoforms in pediatric B cell acute lymphoblastic leukemia (B-ALL).

Methods

We performed the transcriptomic analysis of TP53 isoforms expression in publicly available datasets followed by RT-qPCR in our cohort of pediatric B-ALL and correlated with various clinical and hematological parameters.

Results

Transcriptomic data on B-ALL available online showed overexpression of p53α in B-ALL cases at diagnosis while Δ40p53, p53β and Δ133p53 were downregulated in cases at relapse. In our cohort data (n = 99) at diagnosis, we found the upregulation of the long isoform p53α in 65.65% of patients and the short isoforms Δ133p53 in 61.61% patients and Δ40p53 in 27.27% of the patients, respectively. The over-expression of p53γ and p53β was noted in 19.19% and 14.14% of patients, respectively. To check if TP53 gene mutation contributed to this dysregulated isoform expression, we analysed the whole exome data of our B-ALL patients (n = 88). As expected only 3.7% of patients showed mutation in TP53 gene. Further, we analysed the correlation with various clinical parameters and found positive association of Δ133p53 with ETV6::RUNX1 gene fusion (p = 0.032) which is a known marker of good prognosis in B-ALL. To further validate this observation, we enrolled B-ALL relapse cases (n = 46) where samples at diagnosis were also available (n = 12). Analysis of TP53 isoforms expression in relapse B-ALL patients showed significant reduction in the expression of short isoforms of TP53 i.e. Δ133p53 (p = 0.0036) and Δ40p53 (p = 0.032).

Conclusion

Our data show that TP53 isoforms are dysregulated in B-ALL at diagnosis as well as at relapse. Short TP53 isoforms, particularly Δ133p53 is associated with better prognosis suggesting its potential role in refining risk stratification of B-ALL.