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ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway

Jinqiong Jiang1, Yiping Liu1, Youhong Tang1

  • 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Oncotargets and Therapy
|September 14, 2016
PubMed

Insights

Aldehyde dehydrogenase 1A1 (ALDH1A1) promotes chemoresistance in diffuse large B-cell lymphoma (DLBCL) by activating the JAK2/STAT3 pathway. Targeting ALDH1A1 may overcome resistance to CHOP chemotherapy in DLBCL patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Chemoresistance is a significant challenge in treating diffuse large B-cell lymphoma (DLBCL), leading to treatment failure in a subset of patients.
  • Aldehyde dehydrogenase 1A1 (ALDH1A1) is increasingly recognized as a key enzyme involved in tumor chemoresistance.
  • Understanding the role of ALDH1A1 in DLBCL chemoresistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the clinical significance of ALDH1A1 expression in DLBCL patients treated with CHOP chemotherapy.
  • To elucidate the underlying molecular mechanism by which ALDH1A1 contributes to CHOP resistance in DLBCL cells.
  • To explore the potential of targeting ALDH1A1 or its associated pathways to overcome chemoresistance.

Main Methods:

  • Immunohistochemistry was used to assess ALDH1A1 expression in 88 DLBCL tissue samples.
  • Functional assays, including gene overexpression and short hairpin RNA (shRNA) silencing, were performed in DLBCL cell lines (Pfeiffer cells).
  • The JAK2/STAT3 signaling pathway was analyzed, and its role in ALDH1A1-mediated chemoresistance was investigated using pathway inhibitors.

Main Results:

  • ALDH1A1 expression was upregulated in DLBCL patients with stable or progressive disease post-CHOP treatment.
  • Higher ALDH1A1 expression correlated with poorer survival outcomes in DLBCL patients receiving CHOP chemotherapy.
  • Overexpression of ALDH1A1 conferred resistance to CHOP, while its silencing sensitized cells to CHOP; this effect was mediated through the JAK2/STAT3 pathway.

Conclusions:

  • ALDH1A1 is significantly associated with chemoresistance and poor prognosis in DLBCL patients treated with CHOP.
  • ALDH1A1 induces resistance to CHOP chemotherapy in DLBCL by activating the JAK2/STAT3 signaling pathway.
  • Targeting ALDH1A1 presents a promising therapeutic strategy for overcoming CHOP resistance in DLBCL.
Keywords:
ALDH1A1CHOPJAK2/STAT3 pathwaychemoresistancediffuse large B-cell lymphoma

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