Refine
Document Type
- Article (2) (remove)
Language
- English (2)
Has Fulltext
- yes (2)
Is part of the Bibliography
- no (2) (remove)
Keywords
- ALL (2) (remove)
Institute
- Medizin (2)
The view that tumors consist of a homogenous mass of clonal derived cells has dramatically changed in recent years. Tumors harbor an enormous heterogeneity of cells with distinct capabilities and functions. The heterogeneity originates from a differentiation hierarchy of tumor cells, similar to normal tissue organization of stem-cell driven organs, but also from clonal succession of subpopulations by randomly acquired genetic mutations and epigenetic changes. Both scenarios are certainly not mutually exclusive, and also stem and progenitor cells underlie mutational selection. Intratumoral heterogeneity is a major challenge for cancer treatment and disease monitoring. Functional studies revealed that not all tumor cells have the same ability to initiate tumor growth upon transplantation in receptive animal models. The tumorinitiating cells (TICs) were called cancer stem cells due to their similarities to normal tissue stem cells in their molecular and functional properties. They can renew themselves long-term and give rise to tumor cells lacking cancer stem cell properties. However, it is worth stressing here that TICs do not necessarily originate from stem cells, but may have regained stem cell properties. TICs caught major attention since they may provide important steps in the progression of malignant diseases, such as epithelial-to-mesenchymal transition, dissemination, long-term persistence, therapy resistance, and relapse of the disease. The prospective identification of TICs using distinct surface markers would allow their molecular and functional characterization, the design of detection methods for diagnosis and prognosis, and the development of targeted therapies against these detrimental cells. While functional evidence for the existence of TICs were provided for many tumor entities, their marker profile still remains largely undefined and controversial. ...
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (~ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.