Prognostic significance of combined BAALC and MN1 gene expression level in acute myeloid leukemia with normal karyotype

Abstract

Introduction: Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes.

Methods: In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential.

Results: BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC⁺ /or MN1⁺ status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1^wt status (P < .001). Therefore, among BAALC⁺ /or MN1⁺ patients the most frequent ones were FLT3-ITD^- /NPM1^- double negative patients with intermediate prognosis. When BAALC⁺ /or MN1⁺ patients were divided into BAALC^high /BAALC^low (21/21) and MN1^high /MN1^low (21/22) groups, we detected that BAALC^high /or MN1^high patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC^high /or MN1^high patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD^- /NPM1^- group of patients that are lacking reliable prognostic markers, where OS in BAALC^high /or MN1^high was only 5 months vs 25 months in BAALC^low /or MN1^low .

Conclusion: These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD^- /NPM1^- patients, transforming this intermediate-risk group, into a group with an adverse prognosis.

Keywords: BAALC gene expression; MN1 gene expression; acute myeloid leukemia; normal karyotype; prognosis.