The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) was determined and several new TPGs were identified and two new MLL rearrangements are now characterized at the molecular level.
The genetic network of reciprocal MLL gene fusions deriving from complex rearrangements is described for the first time, and the distribution of MLL breakpoints for clinical subtypes and fused translocation partner genes (TPGs) will be presented, including novel MLL fusion genes.
The findings of this study further underline the fundamental role of RAF kinase fusion products as a tumor-specific marker and an ideally suited drug target for PA.
The hypothesis is posed that the many different fusion partners of MLL are critically distinct entities for which specific inhibitors should be identified in the future.
A cell line, designated SEM, was established from the peripheral blood of a 5‐year‐old girl in relapse with acute lymphoblastic leukaemia and showed the t(4:11) chromosomal rearrangement, which may have important growth regulatory activities for biphenotypic leukaemic ALL cells.
Improvements made to the existing SB vector system are reported and two new vector types for robust constitutive or inducible expression of any gene of interest are presented, available in 16 variants with different selection marker and fluorescent protein expression to fit most experimental requirements.
It is concluded that translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood, were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by ‘error-prone-repair’ mechanisms, but not by the action of recombinases of the immune system.
This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
A set of genomic fragments was isolated that represent a total of 35 exons encompassing > 95% of the protein‐coding region and the 3′‐non‐translated region of the All‐1 gene and form the basis for a greater understanding of the translocations and other structural alterations of the gene that conserve the open reading frame and thus produce presumably oncogenic variants of the ALL‐1 protein.
A new model for the generation ofchromosomal translocations t(4;11) is presented, which poses, that these translocations are reciprocal but not balanced at the fine structure level and that the DNA damage-repair machinery is likely involved in producing the final structure of the translocation breakpoint.