Scholarlink

Background <p>Imatinib has transformed chronic myeloid leukemia treatment, yet early molecular events linking BCR-ABL1 inhibition to leukemic cell fate remain incompletely understood. We investigated whether imatinib induces time-dependent Hippo–YAP transcript changes and delayed microRNA alterations in K562 cells.</p> Methods and Results <p>K562 cells were exposed to imatinib and analyzed using MTT viability assays, morphological assessment, AO/EB staining, intracellular reactive oxygen species measurement, and RT–qPCR profiling of core Hippo pathway genes and selected Hippo-associated microRNAs (<i>n</i> = 3 independent experiments). At 12&#xa0;h, imatinib induced coordinated upregulation of Hippo pathway transcripts. By 48&#xa0;h, Hippo-related mRNA levels largely returned toward baseline, whereas delayed upregulation of Hippo-associated microRNAs emerged. These molecular changes occurred alongside reduced viability, apoptosis-compatible morphological changes, and decreased ROS levels. To provide exploratory translational context, two public CD34⁺ chronic myeloid leukemia microarray datasets were re-analyzed: GSE12211 (paired pre/post imatinib; <i>n</i> = 6 patients) and GSE14671 (responders vs. non-responders; <i>n</i> = 59 patients). These analyses showed heterogeneous, small-magnitude changes in composite Hippo kinase and YAP/TAZ–TEAD output scores after imatinib exposure and no baseline stratification of responders.</p> Conclusions <p>Imatinib exposure in K562 cells is associated with an early Hippo pathway transcript surge followed by delayed microRNA alterations. The CD34⁺ analyses were exploratory and did not validate a uniform primary-sample Hippo–YAP response. Further functional studies are required to determine whether these microRNAs directly regulate Hippo pathway transcripts or influence leukemic cell fate.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Time-resolved Hippo–YAP transcript and microRNA responses to imatinib in K562 chronic myeloid leukemia cells with exploratory analysis of CD34⁺ progenitor transcriptomes

  • 期刊论文

  • 发表日期：

    2026年5月27日

查看全文
  • Soroush Akbari-Ardabili,
  • Safiyeh Aghazadeh,
  • Mehdi Imani

摘要

Background

Imatinib has transformed chronic myeloid leukemia treatment, yet early molecular events linking BCR-ABL1 inhibition to leukemic cell fate remain incompletely understood. We investigated whether imatinib induces time-dependent Hippo–YAP transcript changes and delayed microRNA alterations in K562 cells.

Methods and Results

K562 cells were exposed to imatinib and analyzed using MTT viability assays, morphological assessment, AO/EB staining, intracellular reactive oxygen species measurement, and RT–qPCR profiling of core Hippo pathway genes and selected Hippo-associated microRNAs (n = 3 independent experiments). At 12 h, imatinib induced coordinated upregulation of Hippo pathway transcripts. By 48 h, Hippo-related mRNA levels largely returned toward baseline, whereas delayed upregulation of Hippo-associated microRNAs emerged. These molecular changes occurred alongside reduced viability, apoptosis-compatible morphological changes, and decreased ROS levels. To provide exploratory translational context, two public CD34⁺ chronic myeloid leukemia microarray datasets were re-analyzed: GSE12211 (paired pre/post imatinib; n = 6 patients) and GSE14671 (responders vs. non-responders; n = 59 patients). These analyses showed heterogeneous, small-magnitude changes in composite Hippo kinase and YAP/TAZ–TEAD output scores after imatinib exposure and no baseline stratification of responders.

Conclusions

Imatinib exposure in K562 cells is associated with an early Hippo pathway transcript surge followed by delayed microRNA alterations. The CD34⁺ analyses were exploratory and did not validate a uniform primary-sample Hippo–YAP response. Further functional studies are required to determine whether these microRNAs directly regulate Hippo pathway transcripts or influence leukemic cell fate.