Molecular biology reports · 2026
Increased MYB alternative promoter usage induces daunorubicin resistance in human leukemia cells via ABCA2 upregulation.
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Fang Huiying, Wang Yucheng, Zhou Zhenhua, Li Xinyu, Sun Chang, Zhang Junfang, Han Bingshe
Аннотация
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.
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.