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Updated: Apr 27, 2026

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Distinguishing between cancer cell differentiation and resistance induced by all-trans retinoic acid using

Song-Mei Liu1, Weiping Chen2, Jin Wang3

  • 1Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

Scientific Reports
|July 5, 2014
PubMed

Insights

All-trans retinoic acid (ATRA) resistance in leukemia involves specific gene up-regulation. Understanding these DNA repair pathways can guide new cancer treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • All-trans retinoic acid (ATRA) is effective for cancer treatment but resistance is a significant clinical challenge.
  • Understanding the molecular mechanisms of ATRA resistance is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To identify the molecular mechanisms underlying ATRA resistance in cancer.
  • To investigate the relationship between ATRA-induced differentiation and drug resistance.

Main Methods:

  • Developed a multidrug-resistant leukemia cell line (HL-60[R]) through sequential ATRA exposure.
  • Performed cytotoxicity analysis, comparative genome hybridization, and transcriptional profiling.
  • Conducted functional pathway analysis on identified genes.

Main Results:

  • HL-60[R] cells exhibited resistance to ATRA, doxorubicin, and etoposide.
  • Identified chromosomal gains (4q34, 9q12, 19q13) and a loss (Yq12) in HL-60[R] cells.
  • Found up-regulation of 7 genes (FEN1, RFC5, EXO1, XRCC5, PARP1, POLR2F, GTF2H3) involved in DNA repair pathways (mismatch repair, DNA double-strand break repair, nucleotide excision repair).

Conclusions:

  • Transcriptional profiles and pathway analyses reveal key genes and pathways associated with ATRA resistance.
  • These findings can aid in identifying patients eligible for novel therapeutic strategies in promyelocytic leukemia.

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