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Genomic DNA of leukemic patients: Target for clinical diagnosis of MLL rearrangements
Author(s) -
Meyer Claus,
Kowarz Eric,
Schneider Björn,
Oehm Clarissa,
Klingebiel Thomas,
Dingermann Theo,
Marschalek Rolf
Publication year - 2006
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200600037
Subject(s) - chromosomal translocation , chromosome engineering , biology , breakpoint , minimal residual disease , fusion gene , genetics , myeloid leukemia , computational biology , carcinogenesis , gene , leukemia , cancer research
Genomic DNA is the optimal resource to analyze questions concerning genetic changes that are related to oncogenesis. This article tries to summarize recent efforts to analyze chromosomal changes that trigger the development of human acute myeloid and lymphoblastic leukemias. The aim of this study was to establish an universal method that enables the identification and characterization of chromosomal translocations of the human MLL gene at the genomic nucleotide level. Chromosomal translocations of the MLL gene are the result of illegitimate recombination events in hematopoietic stem or precursor cells, strictly associated with the onset of highly malignant leukemic diseases. The applied technology was able to identify specific fusion alleles that were generated by chromosomal translocations, chromosomal deletions, chromosomal inversions and partial tandem duplications. Moreover, it allowed us to investigate even highly complex genetic changes by applying systematic breakpoint analyses. On the basis of these analyses, patient‐specific molecular markers were established that turned out to be a very good source for monitoring minimal residual disease (MRD). MRD analyses control the efficiency and efficacy of current treatment protocols and have become a very sensitive molecular tool to monitor therapeutic success or failure in individual leukemia patients.