BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2

Abstract

Although the implication of BCL3 has been disclosed in human chronic lymphocytic leukemia as well as other solid tumors, the diagnostic and prognostic of BCL3 expression in acute myeloid leukemia (AML) remains largely unclear. In this study, we isolated total RNA from bone marrow mononuclear cells collected from 101 de novo AML patients and 27 healthy donors. After reverse transcription, quantitative real-time PCR was performed to detect BCL3 expression level. BCL3 mRNA level was significantly down-regulated in BMMCs of AML patients compared with healthy controls (P = 0.0015). BCL3 was showed a higher level in AML patients with poor-risk karyotypes than that of in patients with favorable/intermediate-risk karyotypes (P = 0.014). ROC analysis demonstrated that BCL3 could effectively differentiate AML patients from normal controls. Among the French-American-British (FAB) subtypes, the frequency of low BCL3 expression in M2 subtypes is significantly higher than that of in the other subtypes M1/M4/M5/M6/M7 (P = 0.006), and mildly lower in myelomonocytic/monocytic subtypes M4/M5 (P = 0.064) than those in M1/M2/M6/M7 subtypes. Chromosome analysis revealed that BCL3 low patients had a remarkably higher frequency of t (8;21) abnormality (P = 0.0047) and lower frequency of normal karyotype (P = 0.0059) than BCL3 high patients. BCL3 high patients showed a significantly higher frequency of FLT3-ITD mutation (P = 0.028) and lower frequency of C-Kit mutation (P = 0.0232) than BCL3 low patients. Although there were no significant differences in complete remission and overall survival between BCL3 low and BCL3 high groups, patients with high BCL3 expression markedly shorter overall survival (OS, P = 0.049), relapse-free survival (RFS, P = 0.027) and disease-free survival (DFS, P = 0.042) in M2 AML than low BCL3 expression patients. Additionally, in AMLs of M2 subtype, high BCL3 expression patients had markedly lower complete remission (CR) rate (P = 0.0317) after the second induction treatment than patients with BCL3 low expression. Thus, these findings indicated that BCL3 appeared as a promising molecular biomarker of pediatric acute myeloid leukemia with unfavorable prognosis.