title: Gene expression profiling of adult t(4;11)(q21;q23)-associated acute lymphoblastic leukemia reveals a different signature from pediatric cases.
abstract: Chromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene, located at chromosomal band 11q23, result in the generation of in-frame fusion transcripts with various partner genes from more than 60 distinct gene loci. Among them, the MLL/AFF1 (AF4/FMR2 family, member 1) fusion, associated with rearrangements between bands 4q21 and 11q23 is a recurrent event in pre-B acute lymphoblastic leukemia (ALL). Gene expression profiling (GEP) was performed for four adult patients with ALL. Their signatures were compared to those of ALL patients with a fusion gene involving c-abl oncogene 1, non-receptor tyrosine kinase (ABL1). The comparison of MLL-AFF1 cases with the ABL1 group identified 477 genes being differentially expressed at the statistically significant level of p<0.05, with 296 and 181 genes up- and down-regulated, respectively, in the MLL-AFF1 cases. Three GEP studies on t(4;11)(q21;q23) focusing on the age group of the patients have been reported in the literature. Different expression profiles based on the levels of the homeobox A (HOXA) signature were identified. Although comparison between studies is difficult because of differences in the microarrays and the control samples used, our results and those from the literature suggest that cells carrying t(4;11)(q21;q23) use different pathways to lead to leukemogenesis. Therefore, t(4;11)-associated ALL could represent different biological entities.
authors.affiliation: Faculty of Medicine and Health Sciences, Laboratory of Histology, University of Brest, Brest, France. marc.debraekeleer@univ-brest.fr
authors.forename: Etienne
authors.initials: E
authors.lastname: De Braekeleer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Douet-Guilbert
authors.forename: Marie-Josee
authors.initials: MJ
authors.lastname: Le Bris
authors.forename: Audrey
authors.initials: A
authors.lastname: Basinko
authors.forename: Frederic
authors.initials: F
authors.lastname: Morel
authors.forename: Marc
authors.initials: M
authors.lastname: De Braekeleer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase