Spontaneous apoptosis and BCL2 gene expression as predictors of early death and short overall survival in acute leukemia patients: a prospective, case cohort study

Abstract

Abstract Background 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. Results Early, 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). Conclusion Total 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.

Keywords

• Acute leukemia
• Spontaneous apoptosis
• BCL2
• MCL1
• BCL-XL