The expressions of anti-apoptotic proteins might be associated with the response of venetoclax (VEN)-based therapies in acute myeloid leukemia (AML). Yet, there is not a fast, easy and accurate method to quantitatively detect the expressions of different anti-apoptotic proteins. In this study we combined immunohistochemical staining with immunofluorescence technique to develop a new method of immunofluorescence, and quantitatively detected the expressions of BCL-2, BCL-xL and MCL-1 in bone marrow tissues, and then analyzed the co-relationship between the efficacy of VEN-based therapies and the expressions of the three anti-apoptotic proteins in AML. Bone marrow tissues were obtained from 21 patients with relapsed/refractory (RR)-AML and 16 with newly diagnosed (ND)-AML at diagnosis, remission and relapse, who were treated with VEN-based regimens. First, we confirmed the accuracy and the repeatability of the immunofluorescence method by comparing the consistency of the results being detected by the immunofluorescence and western blotting method, and multi vision detection of the immunofluorescence, respectively. After being confirmed, the detection showed that the median expressions of the three anti-apoptotic proteins in the patients with RR-AML were all higher than that in the ND-AML patients, and the difference in MCL-1 was significant (P=0.004). Also, the median expressions of the three proteins were all higher in the patients without acquiring complete remission (CR) (n=15) compared to those with CR (n=22), and the difference in MCL-1 tended to be significant (P=0.051). In the patients with RR-AML, those with high expressions of BCL-2 had significantly lower CR rate than those with low expressions (P=0.030). Meanwhile, high expressions of MCL-1 tended to be associated with lower CR rate in the patients with either ND-AML (P=0.067) or RR-AML (P=0.063). Furthermore, patients with high expressions of ≥2 anti-apoptotic proteins experienced lower CR rate than those with ≤1 high expression of anti-apoptotic protein. Based on the same patients, the expressions of the three proteins increased if leukemia relapsed or did not acquire response, while they significantly decreased if patients acquired CR. In the patients with ND-AML, the expression of the three proteins presented not obviously impact on the survival, while in the patients with RR-AML, those with high expressions of the three proteins tended to have poorer survival than those with lower expressions. In conclusion, quantitative detection of the expressions of BCL-2, BCL-xL and MCL-1 in bone marrow tissues with the immunofluorescence might predict the efficacy of venetoclax-based therapies in AML.

Key words immunofluorescence, anti-apoptotic protein, venetoclax, acute myeloid leukemia, efficacy

Disclosures

No relevant conflicts of interest to declare.

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2024
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