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BCL6 promotes the methotrexate-resistance by upregulating ZEB1 expression in children with acute B lymphocytic

H-B Wu1, W-F Lv, Y-X Wang

  • 1Children's Health Section, The Children & Women's Healthcare of Laiwu City, Laiwu, China. 13563428066@126.com.

European Review for Medical and Pharmacological Sciences
|September 5, 2018
PubMed

Insights

BCL6 is overexpressed in children with methotrexate-resistant acute lymphoblastic leukemia (B-ALL). This overexpression promotes ZEB1, reducing B-ALL sensitivity to methotrexate.

Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Acute lymphoblastic leukemia (B-ALL) is a common childhood cancer.
  • Methotrexate resistance is a significant challenge in B-ALL treatment.
  • The role of BCL6 in methotrexate resistance in pediatric B-ALL is not fully understood.

Purpose of the Study:

  • To investigate the effect of BCL6 on methotrexate-resistant pediatric B-ALL.
  • To elucidate the underlying molecular mechanism of BCL6's role in B-ALL resistance.

Main Methods:

  • Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to measure BCL6 and E-cadherin expression.
  • Cell cycle and apoptosis assays in methotrexate-resistant B-ALL cells (BALL-1/MTXR) following BCL6 manipulation.
  • Western blot for protein level analysis and Chromatin Immunoprecipitation (ChIP) assay to assess BCL6 binding to the ZEB1 promoter.

Main Results:

  • Higher BCL6 expression was observed in methotrexate-resistant B-ALL bone marrow samples compared to non-resistant samples.
  • BCL6 knockdown in BALL-1/MTXR cells decreased IC50, increased apoptosis, and arrested the cell cycle.
  • BCL6 was found to bind the ZEB1 promoter, promoting ZEB1 expression and influencing E-cadherin levels.

Conclusions:

  • BCL6 is overexpressed in methotrexate-resistant pediatric B-ALL.
  • BCL6 contributes to methotrexate resistance by promoting ZEB1 expression.
  • Targeting BCL6 may offer a therapeutic strategy to overcome methotrexate resistance in B-ALL.
Abstract

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