BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia

摘要

High brain and acute leukemia, cytoplasmic ( BAALC ) expression defines an important risk factor in cytogenetically normal acute myeloid leukemia (CN-AML). The prognostic value of BAALC expression in relation to other molecular prognosticators was analyzed in 326 CN-AML patients ( BAALC expression was associated with prognostically adverse mutations: FLT3 internal tandem duplication ( FLT3 -ITD) with an FLT3 -ITD/ FLT3 wild-type (wt) ratio of ?0.5 ( P =0.001), partial tandem duplications within the MLL gene ( MLL -PTD) ( P =0.002), RUNX1 mutations (mut) ( P WT1 mut ( P =0.001), while it was negatively associated with NPM1 mut ( P BAALC expression was also associated with prognostically favorable biallelic CEBPA ( P =0.001). Survival analysis revealed an independent adverse prognostic impact of high BAALC expression on overall survival (OS) and event-free survival (EFS), and also on OS when eliminating the effect of allogeneic stem cell transplantation (SCT) (OSTXcens). Furthermore, we analyzed BAALC expression in 416 diagnostic and follow-up samples of 66 patients. During follow-up, BAALC expression correlated with mutational load or expression levels, respectively, of other minimal residual disease markers: FLT3 -ITD ( r =0.650, P MLL -PTD ( r =0.728, P NPM1 mut ( r =0.599, P RUNX1 mut ( r =0.889, P BAALC expression after the second cycle of induction chemotherapy was associated with improved EFS. Thus, our data underline the utility of BAALC expression as a marker for prognostic risk stratification and detection of residual disease in CN-AML.