Zhongguo quanke yixue (Jun 2024)
Correlation between Bcl-2 Expression and the Efficacy of Bcl-2 Inhibitors in Patients with Myelodysplastic Syndromes
Abstract
Background The heterogeneity of myelodysplastic syndromes (MDS) is strong, with poor efficacy of existing therapeutic regimens and large individual differences in patient prognosis. B-cell lymphomato-2 (Bcl-2) protein is highly expressed in patients with myeloid tumors, which has been proved by previous to be associated with disease progression, chemotherapy resistance, and shortened overall survival. The Bcl-2 inhibitor Veneckla (VEN) is approved for elderly patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive therapy, and there is less data on its use in MDS patients. The difference in Bcl-2 expression in MDS patients and its correlation with the efficacy and prognosis of VEN therapy haven't been reported. Objective To analyse the expression of Bcl-2 protein in MDS patients and assess its correlation with the efficacy and prognosis of VEN treatment. Methods The clinical data of 71 patients with MDS admitted to Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital from July 2018 to December 2022 were retrospectively analyzed. Baseline data of patients including gender, age, blood routine, blood biochemistry, bone marrow hemocytology, flow cytometry, chromosome karyotype, myeloid gene mutation, fusion gene mutation and MDS-EB typing were collected. The expression of Bcl-2 protein was detected by immunohistochemical staining. According to the modified International Prognostic Score System (IPSS-R), the patients were divided into 5 risk levels of very low risk (0 case), low risk (1 case), medium risk (7 cases), high risk (40 cases) and very high risk (23 cases). Patients with bone marrow Bcl-2 positivity≥10% were defined as Bcl-2 positive and<10% as Bcl-2 negative. Patients were divided into the positive group (n=38) and negative group (n=33). Of 63 patients with high-risk and very high-risk MDS, 38 were treated and evaluated for efficacy, including 28 patients who received VEN combined with azacitidine (VA combination regimen) and 10 patients who received hypomethylated drugs (HMA, including azacitidine or decitabine) as monotherapy. The patients were followed up until 2022-12-30. Kaplan-Meier curve was plotted to analyze the overall survival time (OS) of different patients, and Log-rank test was used for comparison. Univariate Cox regression model was used to analyze the influencing factors of patients' OS. Results The proportions of fusion gene mutation and nuclear myeloid phosphoprotein 1 (NPM1) gene mutation in the positive group were higher than those in the negative group, and the difference was statistically significant (P<0.05). Of the 10 patients who received HMA monotherapy, 1 was Bcl-2 negative and 9 were Bcl-2 positive, after 14 days of treatment, 4 of them (40.0%) achieved composite complete response (CR/mCR). Of the 28 patients receiving the VA combination regimen, 12 were Bcl-2 negative and 16 were Bcl-2 positive, and after 14 days of treatment, 20 (71.4%) patients receiving the VA combination regimen achieved CR/mCR. There was no significant difference in CR/mCR ratio between the two treatment regimens (P=0.087). The median overall survival time (mOS) for patients with VA combination therapy was 6.9 months, with a mOS of 2.9 months for Bcl-2 negative patients and 7.4 months for Bcl-2 positive patients. There was no significant difference in survival rate between Bcl-2 positive patients and Bcl-2 negative patients (χ2=2.075, P=0.150). The mOS of Bcl-2 positive patients receiving HMA monotherapy was 4.3 months, and there was no significant difference in the survival rate comparing with Bcl-2 positive patients receiving VA combination regimen (χ2=0.824, P=0.364). Univariate Cox regression model analysis showed that age, Bcl-2 protein expression, mutant gene number, chromosome karyotype, MDS-EB typing, IPSS-R risk, and efficacy were not the influencing factors for OS in patients treated with VA combination regimen (P>0.05) . Conclusion Bcl-2 protein contributes to MDS fusion gene mutation and myeloid gene mutation; Bcl-2 positive expression was not associated with the survival of MDS patients. There was no difference in survival rate between Bcl-2 positive and Bcl-2 negative patients who received the VA combination regimen.
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