Genomic DNA of leukemic patients: target for clinical diagnosis of MLL rearrangements.
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.
Meyer
Claus
C
Institute of Pharmaceutical Biology, ZAFES, Diagnostic Center of Acute Leukemia, JWG-University of Frankfurt, Biocenter, Frankfurt/Main, Germany.
Kowarz
Eric
E
Schneider
Björn
B
Oehm
Clarissa
C
Klingebiel
Thomas
T
Dingermann
Theo
T
Marschalek
Rolf
R
D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005858:Germany / Q000453:epidemiology; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D005819:Genetic Markers; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase