title: Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement.
abstract: The aim of this study was to identify immunobiological subgroups in 133 infant acute lymphoblastic leukemia (ALL) cases as assessed by their immunophenotype, immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement pattern, and the presence of mixed lineage leukemia (MLL) rearrangements. About 70% of cases showed the pro-B-ALL immunophenotype, whereas the remaining cases were common ALL and pre-B-ALL. MLL translocations were found in 79% of infants, involving MLL-AF4 (41%), MLL-ENL (18%), MLL-AF9 (11%) or another MLL partner gene (10%). Detailed analysis of Ig/TCR rearrangement patterns revealed IGH, IGK and IGL rearrangements in 91, 21 and 13% of infants, respectively. Cross-lineage TCRD, TCRG and TCRB rearrangements were found in 46, 17 and 10% of cases, respectively. As compared to childhood precursor-B-ALL, Ig/TCR rearrangements in infant ALL were less frequent and more oligoclonal. MLL-AF4 and MLL-ENL-positive infants demonstrated immature rearrangements, whereas in MLL-AF9-positive leukemias more mature rearrangements predominated. The immature Ig/TCR pattern in infant ALL correlated with young age at diagnosis, CD10 negativity and predominantly with the presence and the type of MLL translocation. The high frequency of immature and oligoclonal Ig/TCR rearrangements is probably caused by early (prenatal) oncogenic transformation in immature B-lineage progenitor cells with germline Ig/TCR genes combined with a short latency period.
authors.affiliation: Department of Immunology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: M W J C
authors.initials: MW
authors.lastname: Jansen
authors.forename: L
authors.initials: L
authors.lastname: Corral
authors.forename: V H J
authors.initials: VH
authors.lastname: van der Velden
authors.forename: R
authors.initials: R
authors.lastname: Panzer-Grümayer
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: A
authors.initials: A
authors.lastname: Schrauder
authors.forename: R
authors.initials: R
authors.lastname: Marschalek
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: M L
authors.initials: ML
authors.lastname: den Boer
authors.forename: W J C
authors.initials: WJ
authors.lastname: Hop
authors.forename: M G
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: A
authors.initials: A
authors.lastname: Biondi
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D011948:Receptors, Antigen, T-Cell; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase