TY - JOUR
T1 - Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement
AU - Jansen, M W J C
AU - Corral, L
AU - van der Velden, V H J
AU - Panzer-Grümayer, R
AU - Schrappe, M
AU - Schrauder, A
AU - Marschalek, R
AU - Meyer, C
AU - den Boer, M L
AU - Hop, W J C
AU - Valsecchi, M G
AU - Basso, G
AU - Biondi, A
AU - Pieters, R
AU - van Dongen, J J M
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Gene Expression Regulation, Neoplastic
KW - Gene Frequency
KW - Gene Rearrangement
KW - Genes, Immunoglobulin
KW - Histone-Lysine N-Methyltransferase
KW - Humans
KW - Immunophenotyping
KW - Myeloid-Lymphoid Leukemia Protein/genetics
KW - Polymerase Chain Reaction
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
KW - Receptors, Antigen, T-Cell/genetics
KW - Translocation, Genetic
UR - http://www.scopus.com/inward/record.url?scp=33947430631&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2404578
DO - 10.1038/sj.leu.2404578
M3 - Article
C2 - 17268512
SN - 0887-6924
VL - 21
SP - 633
EP - 641
JO - Leukemia
JF - Leukemia
IS - 4
ER -