Kategorie: Maligní lymfomy a leukémie
Téma: Acute myeloid leukemia - Clinical 2
Číslo abstraktu: 0068
Autoři: Malou C.H. Hermkens; MD Marry M. van den Heuvel-Eibrink, PhD; Susan T.C.J.M. Arentsen-Peters; A. Baruchel; prof. MUDr. Jan Starý, DrSc.; MD Dirk Reinhardt, PhD; Martin Zimmermann, Ph.D.; MD Valerie de Haas, Ph.D.; Prof. MD Rob Pieters, PhD; MD Christian Michel Zwaan, PhD
Background. Pediatric AML is curable in approximately 70% of patients. Its prognosis is determined by genetic aberrations and early treatment response, although 20% of pediatric patients lack cytogenetic aberrations (CN-AML). In adult CN-AML patients, prognosis is worse when there is high expression of either BAALC (Brain And Acute Leukemia Cytoplasmic; chromosome 8q22) or ERG (E26 transformation-specific-related; chromosome 21q22). Aims. We studied expression levels of BAALC and ERG in children in different cytogenetic subgroups aimed at improving risk group stratification and thereby also riskadapted treatment and survival in this subgroup. Methods. Using gene expression profiling (Affymetrix Human Genome U133 Plus 2.0 Array) we studied BAALC and ERG expression in 294 de novo pediatric AML patients, who had been fully characterized for molecular aberrations. Validation was done using RT-qPCR, where we found high correlations between GEP and RT-qPCR for BAALC (Rs=0.809, P<0.001) and ERG (Rs=0.798, P<0.001) expression levels. BAALChigh was defined as above-median and ERGhigh as above the 75th percentile. Results. The CBF-AML group had significantly higher BAALC expression levels (P<0.001) than non-CBF-AML. However, there was no difference in expression levels between the CN-AML group and all other cases. ERG expression levels were found to be higher in t(15;17) cases (P<0.001) than in all other cases. ERG expression was not associated with outcome in any subgroup, nor in the total cohort. In CN-AML, high BAALC expression was a poor prognostic factor for OS (BAALChigh vs BAALClow; 47±11% vs. 76±10%; P=0.03), and a trend for EFS (29±10% vs. 50±11%; P=0.07) and CIR (62±11% vs. 37±10%; P=0.07). However, multivariate analysis, including NUP98/NSD1 translocations and NPM1 mutations, did not identify BAALC expression as an independent risk factor for OS in CN-AML.Summary/ Conclusions. Hence we conclude that BAALC and ERG expression have no prognostic significance in pediatric AML.
Haematologica, 2012; 97(s1): 27
Datum přednesení příspěvku: 14. 6. 2012