title: Gene expression profiling-based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants.
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 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 MLL translocations. Our data show that MLL germline 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 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.
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. r.stam@erasmusmc.nl
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Stam
authors.forename: Pauline
authors.initials: P
authors.lastname: Schneider
authors.forename: Jill A P
authors.initials: JA
authors.lastname: Hagelstein
authors.forename: Marieke H
authors.initials: MH
authors.lastname: van der Linden
authors.forename: Dominique J P M
authors.initials: DJ
authors.lastname: Stumpel
authors.forename: Renee X
authors.initials: RX
authors.lastname: de Menezes
authors.forename: Paola
authors.initials: P
authors.lastname: de Lorenzo
authors.forename: Maria G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D011495:Histone-Lysine N-Methyltransferase; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000096:biosynthesis* / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D012307:Risk Factors; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; C088144:HoxA protein; D011495:Histone-Lysine N-Methyltransferase