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Background <p>MYB is a key transcriptional regulator of hematopoietic cell proliferation, survival, and lineage commitment. Aberrant MYB activity has been linked to hematologic malignancies and clinically relevant features, including poor prognosis and drug resistance. However, the mechanisms by which MYB contributes to drug resistance in leukemia remain unclear.</p> Methods and Results <p>Here, we show that altered <i>MYB</i> alternative promoter usage may contribute to DNR resistance in leukemia cells, at least in part through ABCA2 upregulation. CCK8 assays showed that ΔN MYB promoted leukemia cell proliferation and enhanced DNR resistance more potently than full-length MYB. RT-qPCR showed that both full-length MYB and ΔN MYB up-regulated ABC transporter genes, with ΔN MYB exerting a stronger effect than full-length MYB and ABCA2 showing the most pronounced increase. RT-qPCR analysis of DNR-resistant leukemia cells showed no obvious change in total <i>MYB</i> expression and <i>MYB</i> exon 2 level, whereas <i>MYB</i> exon 1 level was decreased, the <i>MYB</i> exon 2/exon 1 ratio and ABCA2 expression were markedly increased. Rescue experiments showed that ABCA2 knockdown partially reversed the proliferation-promoting and DNR-resistant effects of ΔN MYB in leukemia cells.</p> Conclusions <p>These findings suggest that increased <i>MYB</i> TSS2-associated transcription contributes to DNR resistance in human leukemia cells, potentially through ΔN MYB-associated ABCA2 upregulation. This pathway may represent a potential therapeutic target for overcoming DNR resistance in leukemia.</p>

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Increased MYB alternative promoter usage induces daunorubicin resistance in human leukemia cells via ABCA2 upregulation

  • 期刊论文

  • 发表日期：

    2026年7月18日

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  • Huiying Fang,
  • Yucheng Wang,
  • Zhenhua Zhou,
  • Xinyu Li,
  • Chang Sun,
  • Junfang Zhang,
  • Bingshe Han

摘要

Background

MYB is a key transcriptional regulator of hematopoietic cell proliferation, survival, and lineage commitment. Aberrant MYB activity has been linked to hematologic malignancies and clinically relevant features, including poor prognosis and drug resistance. However, the mechanisms by which MYB contributes to drug resistance in leukemia remain unclear.

Methods and Results

Here, we show that altered MYB alternative promoter usage may contribute to DNR resistance in leukemia cells, at least in part through ABCA2 upregulation. CCK8 assays showed that ΔN MYB promoted leukemia cell proliferation and enhanced DNR resistance more potently than full-length MYB. RT-qPCR showed that both full-length MYB and ΔN MYB up-regulated ABC transporter genes, with ΔN MYB exerting a stronger effect than full-length MYB and ABCA2 showing the most pronounced increase. RT-qPCR analysis of DNR-resistant leukemia cells showed no obvious change in total MYB expression and MYB exon 2 level, whereas MYB exon 1 level was decreased, the MYB exon 2/exon 1 ratio and ABCA2 expression were markedly increased. Rescue experiments showed that ABCA2 knockdown partially reversed the proliferation-promoting and DNR-resistant effects of ΔN MYB in leukemia cells.

Conclusions

These findings suggest that increased MYB TSS2-associated transcription contributes to DNR resistance in human leukemia cells, potentially through ΔN MYB-associated ABCA2 upregulation. This pathway may represent a potential therapeutic target for overcoming DNR resistance in leukemia.