BAALC expression as a predictor of primary response to treatment in childhood Acute Lymphoblastic Leukemia

LEONARDI, DAIANA BEATRIZ; COTIGNOLA, JAVIER HERNÁN; BRANDANI, JAVIER NAHUEL; ABBATE, MERCEDES; VAZQUEZ, ELBA SUSANA

Mar del Plata

Congreso; LXI Reunión Científica anual de la Sociedad Argentina de la Investigación Clínica. SAIC; 2016

SAIC

Current treatment protocols for Acute Lymphoblastic Leukemia (ALL)include an initial stratification of patients into groups of risk for diseaserelapse in order to receive the most appropriate treatment protocol and toreduce the number of relapses and therapy failure. This stratification is basedon biochemical and cytogenetic parameters at diagnosis, and the early responseto treatment determined by the minimal residual disease. However, there arestill some patients that recur in all risk groups. Many studies suggest that theinclusion of gene variants and expression profiling during initialstratification is a promising field. It has been reported an associationbetween BAALC (brain and acute leukemia, cytoplasmatic) over-expression andpoor prognosis in Acute Myeloid Leukemia. Thus, we aimed to evaluate theprognostic value of BAALC in childhood ALL. We studied the expression levels of BAALC using public repositories of expression microarrays and a Bioconductor-based analysis. All studies included pediatric ALL samples. In two studies (GSE39339, GSE141618) we found that poor/non-responders (>25% of blast in bone marrow (M3) after the first cycle of chemotherapy) expressed higher BAALC levels at diagnosis (fold-change (FC) = 5.3; p=0.002; and FC=3.1; p=0.01; respectively) compared with good responders (bone marrow M1/M2). In addition, patients who failed to achieve complete remission during induction showed a 4-fold increase in BAALC expression compared to patients who reached complete remission and relapsed within 4 years (p=0.01). In other studies (GSE19143, GSE5820, GSE646_647) that analyzed if primary ALL samples were sensitive or resistant to ex vivo treatment with glucocorticoids we observed a trend for higher BAALC expression in resistant samples (FC=1.6; p=0.05). These results suggest that the inclusion of BAALC expression profile at diagnosis of childhood ALL could improve the initial stratification and, in consequence, improve therapy response and survival.