Browsing by Author "Marschalek, R."

Derivative chromosomes of 40 patients diagnosed with t(4;11) acute lymphoblastic leukemia (ALL),were analysed on the genomic DNA level. Chromosomal breakpoints were identified in most cases within the known breakpoint cluster regions of the involved MLL and AF4 genes, Due to our current knowledge of the primary DNA sequences of both breakpoint cluster regions, specific features were identified at the chromosomal fusion sites, including deletions, inversions and duplications of parental DNA sequences, After separation of all t(4;11) leukemia patients into two age classes (below and above 1 year of age), the analysis of chromosomal fusion sites revealed significant differences in the distribution of chromosomal breakpoints and led to the definition of two hotspot areas within the MLL breakpoint cluster region, This may point to the possibility of different age-linked mechanisms that sere leading to t(4;11) chromosomal translocations. Oncogene (2001) 20, 2900-2907.

Childhood acute lymphoblastic leukemia (ALL) Is frequently initiated in utero at a time of developmentally regulated insertion of N regions into the DJ(H) rearrangements of immunoglobulin heavy-chain (Ig(H)) genes. Here it is shown that N regions are present In the clonotypic DJ(H) rearrangements In 11 of 12 infant ALLs with t(4;11). These data are compared with the 122 previously published DJ(H) sequences and were found to have a pattern similar to that of ALL in children older than 3 years at diagnosis but were unlike that in children younger than 3 years who predominantly lack N regions. These findings, therefore, indicate that t(4;11)-positive infant ALL is initiated later in fetal development than most B-cell precursor ALL from children younger than 3 years and that they have a shorter latency period already in utero. (C) 2001 by The American Society of Hematology.