Acute lymphoblastic leukemia (ALL) in infants (< 1 year) is characterized by a poor prognosis and a high incidence of MLL translocations. 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 MLL translocation, whereas the analysis of translocationnegative 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 MLL translocations. Our data show that MLL germline infant ALL specifies a gene expression pattern that is different from both MLL-rearranged infantALL 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 MLL translocation 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 HOXA expression, and that patients lacking HOXA expression 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.

Stam, R., Schneider, P., Hagelstein, J., van der Linden, M., Stumpel, D., de Menezes, R., et al. (2010). Gene expression profiling–based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants. BLOOD, 115(14), 2835-2844 [10.1182/blood-2009-07-233049].

Gene expression profiling–based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants

VALSECCHI, MARIA GRAZIA;
2010

Abstract

Acute lymphoblastic leukemia (ALL) in infants (< 1 year) is characterized by a poor prognosis and a high incidence of MLL translocations. 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 MLL translocation, whereas the analysis of translocationnegative 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 MLL translocations. Our data show that MLL germline infant ALL specifies a gene expression pattern that is different from both MLL-rearranged infantALL 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 MLL translocation 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 HOXA expression, and that patients lacking HOXA expression 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.
Articolo in rivista - Articolo scientifico
ALL; infants; gene expression profile
English
2010
115
14
2835
2844
none
Stam, R., Schneider, P., Hagelstein, J., van der Linden, M., Stumpel, D., de Menezes, R., et al. (2010). Gene expression profiling–based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants. BLOOD, 115(14), 2835-2844 [10.1182/blood-2009-07-233049].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/12293
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