Related Experiment Video
Updated: Aug 13, 2026
Investigation of Genetic Dependencies Using CRISPR-Cas9-based Competition Assays
Published on: January 7, 2019
[The effects of Mcl-1 gene on ATRA-resistant HL-60 cell]
Jin-rong Fu1, Wen-li Liu, Jian-feng Zhou
1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Objective:
To investigate the role of Mcl-1 gene in resistance of all-trans retinoic acid (ATRA) of leukemia cells.
Methods:
Long-term, intermittent and repetitive exposure of HL-60 cells to ATRA was used to establish a multidrug-resistance cell line (HL-60/ATRA). HL-60/ATRA cells were transfected with Mcl-1 small interference RNA (siRNA) by Lipofectamine 2000. Western blot was used to detect the expression of Mcl-1. The proliferation, apoptosis and differentiation were evaluated by MTT assay, in situ nick end-labeling (TUNEL) and NBT assay, respectively.
Results:
The HL-60/ATRA could keep its undifferentiated and proliferative status to a high concentration of ATRA (100 nmol/L) with highly expressed Mcl-1 protein (relative grey scale 0.624 +/- 0.127). Mcl-1 gene knockdown by siRNA (relative grey scale 0.267 +/- 0.086) could reverse the resistance of ATRA of HL-60/ATRA by inhibiting proliferation, and inducing differentiation and apoptosis [apoptosis rate (18.5 +/- 4.5)%].
Conclusion:
Mcl-1 gene might be involved in ATRA resistance in HL-60 cells and inhibiting its expression could be a new approach to ATRA resistance reversion.
Insights
The Mcl-1 gene plays a role in leukemia cell resistance to all-trans retinoic acid (ATRA). Inhibiting Mcl-1 gene expression can reverse this resistance, offering a potential new treatment strategy.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Context:
- Acute promyelocytic leukemia (APL) treatment often involves all-trans retinoic acid (ATRA).
- Leukemia cells can develop resistance to ATRA, limiting treatment efficacy.
- The Mcl-1 gene's role in this resistance is not fully understood.
Purpose:
- To investigate the involvement of the Mcl-1 gene in ATRA resistance in leukemia cells.
- To determine if targeting Mcl-1 can overcome ATRA resistance.
Summary:
- A multidrug-resistant leukemia cell line (HL-60/ATRA) was established and showed high Mcl-1 protein expression.
- Knockdown of Mcl-1 using small interference RNA (siRNA) in HL-60/ATRA cells reversed ATRA resistance.
- Mcl-1 inhibition reduced proliferation and induced differentiation and apoptosis in resistant cells.
Impact:
- Mcl-1 gene expression is implicated in ATRA resistance in HL-60 leukemia cells.
- Inhibiting Mcl-1 offers a potential therapeutic strategy to overcome ATRA resistance in leukemia.
- This finding could lead to novel treatment approaches for patients with resistant leukemia.
