Abstract
BackgroundSpontaneous apoptosis and expression of MCL1, BCL2, and BCL-XL may be useful prognostic markers in acute leukemia patients. The purpose of this study is to examine the prognosis in adult leukemia patients based on spontaneous apoptosis and anti-apoptosis gene expressions in circulating leukocytes.ResultsEarly, late, and total apoptosis were significantly increased in peripheral blood leukocytes from patients diagnosed with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) compared to controls and in cases of ALL versus AML (P < 0.001). Total apoptosis decreased significantly in AML and ALL patients who died early (ED); P = 0.001 and P = 0.002, respectively. Anti-apoptosis genes MCL1, BCL2, and BCL-XL were upregulated in 62.4%, 64.2%, and 62.4% of the acute leukemia patients, respectively. Among the AML patients, the up-regulation of BCL2 was paradoxically associated with increased apoptosis and low rates of ED. The expression levels of MCL1 and BCL-XL had no significant prognostic values; among patients diagnosed with non-acute promyelocytic leukemia (non-APL-AML), total spontaneous apoptosis, expression of BCL2, and performance status were independent predictors of overall survival (OS).ConclusionTotal spontaneous apoptosis and BCL2 gene expression may be valuable independent markers for OS in patients with non-APL-AML. Moreover, in ALL patients decreased levels of spontaneous apoptosis were associated with ED, although this was not a significant predictor of OS.
Highlights
Spontaneous apoptosis and expression of myeloid-cell leukemia 1 (MCL1), B-cell lymphoma 2 (BCL2), and B-cell lymphoma-extra-large (BCL-XL) may be useful prognostic markers in acute leukemia patients
Kaplan–Meier analysis with log-rank test and Cox regression analysis were performed to evaluate the impact on Patient characteristics Ninety-eight newly diagnosed adult acute leukemia patients were enrolled in this study, 70 patients diagnosed with acute myeloid leukemia (AML), and 28 with acute lymphoblastic leukemia (ALL). 61 of the patients were male (62.2%) and 37 were female (37.8%). 15 healthy participants were included in this study; 8 of them were male (53.3%) and 7 female (46.7%)
No significant differences were observed regarding the expression of anti-apoptotic genes in comparison between acute leukemia patients and controls or between those diagnosed with AML versus ALL (Table 1 and Additional file 1: Supplementary Figure 1)
Summary
Spontaneous apoptosis and expression of MCL1, BCL2, and BCL-XL may be useful prognostic markers in acute leukemia patients. The purpose of this study is to examine the prognosis in adult leukemia patients based on spontaneous apoptosis and anti-apoptosis gene expressions in circulating leukocytes. Apoptosis is the process of programed cell death that plays an important role in controlling cellular differentiation and proliferation. Among these roles, leukemic cells with alterations in one or both of the apoptotic pathways can acquire a survival advantage over their normal counterparts and can develop resistance to chemotherapeutic drugs. Despite the advancements in leukemia therapy, Some recent studies have focused on the role of spontaneous and/or treatment-induced cellular apoptosis for risk stratification of acute leukemia patients. Assays that detect cell surface Annexin V in combination with
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