| Autor: |
Stam, Ronald W., Schneider, Pauline, Hagelstein, Jill A.P., van der Linden, Marieke H., Stumpel, Dominique J.P.M., de Menezes, Renee X., de Lorenzo, Paola, Valsecchi, Maria G., Pieters, Rob |
| Zdroj: |
Blood; April 2010, Vol. 115 Issue: 14 p2835-2844, 10p |
| Abstrakt: |
Acute lymphoblastic leukemia (ALL) in infants (< 1 year) is characterized by a poor prognosis and a high incidence of MLLtranslocations. Several studies demonstrated the unique gene expression profile associated with MLL-rearranged ALL, but generally small cohorts were analyzed as uniform patient groups regardless of the type of MLLtranslocation, whereas the analysis of translocation-negative infant ALL remained unacknowledged. Here we generated and analyzed primary infant ALL expression profiles (n = 73) typified by translocations t(4;11), t(11;19), and t(9;11), or the absence of MLLtranslocations. Our data show that MLLgermline infant ALL specifies a gene expression pattern that is different from both MLL-rearranged infant ALL and pediatric precursor B-ALL. Moreover, we demonstrate that, apart from a fundamental signature shared by all MLL-rearranged infant ALL samples, each type of MLLtranslocation is associated with a translocation-specific gene expression signature. Finally, we show the existence of 2 distinct subgroups among t(4;11)–positive infant ALL cases characterized by the absence or presence of HOXAexpression, and that patients lacking HOXAexpression are at extreme high risk of disease relapse. These gene expression profiles should provide important novel insights in the complex biology of MLL-rearranged infant ALL and boost our progress in finding novel therapeutic solutions. |
| Databáze: |
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