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 BCL3low patients had a remarkably higher frequency of t (8;21) abnormality (P = 0.0047) and lower frequency of normal karyotype (P = 0.0059) than BCL3high patients. BCL3high patients showed a significantly higher frequency of FLT3-ITD mutation (P = 0.028) and lower frequency of C-Kit mutation (P = 0.0232) than BCL3low patients. Although there were no significant differences in complete remission and overall survival between BCL3low and BCL3high 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.
Highlights
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, which comprises approximately 15–20% of pediatric leukemia[1]
The discriminative capacity of BCL3 was revealed by remission characteristic (ROC) curve analysis, and the results indicated that BCL3 with and area under the curve (AUC) value of 0.721 might serve as a potential biomarker for distinguishing between AML and controls (P < 0.001, Fig. 2)
Patients including 45 M2 subtype was obtained from Gene Expression Omnibus data. c and d overall survival and disease-free survival were conducted by the website cBioPortal patients compared to healthy controls
Summary
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, which comprises approximately 15–20% of pediatric leukemia[1]. The cure rate has improved, treatments are associated with notable morbidity and mortality. About 60–70% of patients achieve complete remission after the induction chemotherapy, only 20–30% of patients achieve long-term disease-free survival (DFS) [2,3,4]. Each AML patients can be separated into distinct risk subgroup. The diagnostic classification of pediatric AML depends on the combination of morphology, cytochemistry, immunophenotyping and molecular genetics. Aberrant expression of cancer-related genes has been associated with the prognosis and treatment outcome of AML
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