Relationship between Bax and Bcl-2 Protein Expression and Outcome of Induction Phase Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

Abstract

Background: Overexpression of the antiapoptotic protein Bcl-2 causes apoptosis to stop and conversely the increased expression of the proapoptotic protein Bax makes lymphoblasts easy to destroy. The Bax/Bcl-2 ratio plays a role in the balance of apoptosis, immortality, resistance, and outcome of chemotherapy. We analyzed the relationship between the Bax/BCl-2 ratio and the outcome of induction phase chemotherapy in pediatric Acute Lymphoblastic Leukemia (ALL). Methods: This research was conducted with a prospective observational study on pediatric ALL aged 1-18 years who were newly diagnosed based on bone marrow aspiration (morphology and immunophenotyping) at Dr. Soetomo General Hospital, Surabaya on October 2020 to March 2021. Expression of Bcl-2, Bax, and Bax/Bcl-2 protein ratio was measured by the flow cytometry method from lymphoblast on bone marrow aspirate samples before and after induction phase chemotherapy according to the 2018 Childhood ALL Indonesian Protocol. The outcomes evaluated were survival and remission rate (lymphoblasts in the bone marrow less than 5%). We used the Mann-Whitney U test and Wilcoxon Signed Rank test to analyze the differences between protein expression with p<0.05 for a two-tailed test. Results: We included 17/26 pediatric ALL, consisting of 88% male, 94% LLA-L1, 76% B cell ALL and 24% T cell ALL. Mean expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio before chemotherapy among pediatric ALL who alive (N=11) and dead (N=6) were not significantly different (p>0.05). All children who completed the induction phase of chemotherapy went into remission. Bax and Bcl-2 expression before and after chemotherapy showed no difference (p>0.05). The Bax/Bcl-2 ratio increased from 1.74(SD 1.846) to 6.17(4.139) with p=0.021. Conclusion: Expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio at the beginning of diagnosis did not affect the survival of pediatric ALL after the induction phase of chemotherapy. The Bax/Bcl-2 protein ratio increased 3.5 times in pediatric ALL with remission outcomes, indicating proapoptotic dominance.

Caspase 3 Expressions in Children with Acute Lymphoblastic Leukemia During Induction Phase Chemotherapy

“…Salama et al (40) reported that caspase-3 levels in B-ALL cases showed a higher difference before and after induction chemotherapy compared to T-ALL patients (p=0.025). Gebyarani et al (41) reported different results that the mean expression of caspase-3 after chemotherapy was higher than before chemotherapy with a statistically significant difference (p=0.03). Faderl et al (11) suggested possibility to complete remission was significantly higher in the cut-off of caspase-3 > 0.37.…”

Human Keratinocyte-Derived Exosomal MALAT1 Promotes Diabetic Wound Healing by Upregulating MFGE8 via microRNA-1914-3p

“…Meanwhile, since BAX and Bcl2 are key factors in the process of apoptosis, 61 the correlation and ratio of the two determine the survival or death of cells after apoptotic stimulation. 62 Most of the studies have used the examination of BAX and BCL2 expression levels to verify apoptosis. [61][62][63][64] Therefore, we likewise chose BAX and Bcl-2 as indicators to detect apoptosis.…”

“…62 Most of the studies have used the examination of BAX and BCL2 expression levels to verify apoptosis. [61][62][63][64] Therefore, we likewise chose BAX and Bcl-2 as indicators to detect apoptosis. We found that human monocyte-derived macrophages co-cultured with KCs-oe-MALAT1-Exo possessed greater cytophagocytosis, weaker apoptosis and a greater tendency to polarize towards the M2 phenotype.…”

Risk factors of platelet refractoriness after thrombocyte concentrate transfusion in pediatric acute leukemia

“…ALL is a common malignancy in children, with a 70-90% rate of survival despite chemotherapy failure and relapse (Kapoor and Singh, 2018;Lanzkowsky et al, 2011;Pui et al, 2008). In a study by Cahyadi et al, it's stated that all pediatric ALL who died had thrombocytopenia (Cahyadi et al, 2022).…”