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<p>Acute promyelocytic leukemia (APL) is characterized by the presence of <i>PML::RARA</i> fusion gene, and a favorable response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) administration. Here, we studied the leukemogenic properties of a novel fusion gene, <i>ETV6::RARA</i> t(12;17)(p13;q21), identified in an APL patient lacking the <i>PML::RARA</i> rearrangement. The ETV6-RARA fusion protein was over-expressed via lentiviral transfection in leukemia cells and its effects on cell growth were evaluated with cell counting kit 8 (CCK8) assay and on apoptosis and cellular differentiation with flow cytometry. The expression features induced by ETV6-RARA were studied by whole transcriptomic RNA sequencing analysis. ETV6-RARA over-expression enhanced the differentiation of U937 and HL60 cells to ATRA administration. ATRA, but not ATO, decreased the in-vitro levels of ETV6-RARA protein. ETV6-RARA significantly reduced the proliferation rates of U937 cells as compared to the control. Apoptosis in U937 ETV6-RARA+ cells was induced with combined ATRA and ATO administration. Differential gene expression analysis showed significant up-regulation of RARA in U937 ETV6-RARA+ cells, and gene set enrichment analysis revealed similarity between cells with ETV6::RARA and patients with PML::RARA based on their total RNA expression profiles. Furthermore, the expression profiles of U937 ETV6-RARA+ cells presented the activated enrichment of HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION, and inhibited enrichment of HALLMARK_E2F_TARGETS pathways compared to the control cells. ETV6::RARA is an ATRA/ATO sensitive fusion gene.</p>

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The novel ETV6::RARA fusion gene, identified in acute promyelocytic leukemia, is sensitive to invitro all-tans retinoic acid and arsenic trioxide administrations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月14日

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  • Mohammad Arian Hassani,
  • Dan Huang,
  • Yuan Gao,
  • Xuehong Zhang,
  • Ziheng Tang,
  • Yanan Huang,
  • Yingxin Wang,
  • Xijia Wang,
  • Jinsong Yan

摘要

Acute promyelocytic leukemia (APL) is characterized by the presence of PML::RARA fusion gene, and a favorable response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) administration. Here, we studied the leukemogenic properties of a novel fusion gene, ETV6::RARA t(12;17)(p13;q21), identified in an APL patient lacking the PML::RARA rearrangement. The ETV6-RARA fusion protein was over-expressed via lentiviral transfection in leukemia cells and its effects on cell growth were evaluated with cell counting kit 8 (CCK8) assay and on apoptosis and cellular differentiation with flow cytometry. The expression features induced by ETV6-RARA were studied by whole transcriptomic RNA sequencing analysis. ETV6-RARA over-expression enhanced the differentiation of U937 and HL60 cells to ATRA administration. ATRA, but not ATO, decreased the in-vitro levels of ETV6-RARA protein. ETV6-RARA significantly reduced the proliferation rates of U937 cells as compared to the control. Apoptosis in U937 ETV6-RARA+ cells was induced with combined ATRA and ATO administration. Differential gene expression analysis showed significant up-regulation of RARA in U937 ETV6-RARA+ cells, and gene set enrichment analysis revealed similarity between cells with ETV6::RARA and patients with PML::RARA based on their total RNA expression profiles. Furthermore, the expression profiles of U937 ETV6-RARA+ cells presented the activated enrichment of HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION, and inhibited enrichment of HALLMARK_E2F_TARGETS pathways compared to the control cells. ETV6::RARA is an ATRA/ATO sensitive fusion gene.