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- Title
Identifikace nových molekulárních markerů pro sledování minimální reziduální nemoci u akutních leukemií.
- Authors
T., Jančušková; R., Plachý; J., Štika; L., Krutílková; D. W., Hardekopf; T., Liehr; N., Kosyakova; R., Čmejla; L., Žejšková; T., Kozák; P., Žák; M., Karas; S., Peková
- Abstract
Acute leukaemia (AL) comprises a heterogeneous group of haematological malignancies with varying prognoses. In light of this heterogeneity, individual patient response to treatment can be difficult to predict. Sensitive monitoring of residual leukemic cell populations (minimal residual disease -- MRD) is thus very important and holds great potential for improving treatment strategies. Commonly used MRD targets include recurrent cytogenetic abnormalities and mutations in important haematological genes. Unfortunately, such targets are identified in a majority of adult ALL patients but only in about 50% of adult AML patients. Identification of new specific leukemic blast molecular markers for MRD assessment is therefore highly desirable. Our goal was to develop a unique technical approach for the identification and mapping of clone-specific chromosomal abnormalities down to the single nucleotide level using current molecular cytogenetic techniques, particularly multicolour fluorescence in situ hybridization, multicolour chromosomebanding (mFISH, mBAND)and multiplex hybridization of fluorescently labelled BAC dones (BAC-FISH). Higher resolution was achieved by hybridization of fluorescent probes to combed DNA fibres (molecular combing, fibre-FISH). Another approach used for the precise identification of chromosomal breakpoints was chromosome micro dissection followed by next-generation sequencing (NGS) of the dissected material. Finally, a specific Real-Time PCR assay to monitor MRD was designed. Modern technologies open new vistas for the detection and identification of unique clone-specific abnormalities in AL patients. Our work clearly suggests that mapping from the chromosomal level down to the nucleotide level is feasible and readily applicable in eligible AL patients, allowing its' use in standard clinical practice and as a tool for personalized „tailor-made″ medicine.
- Publication
Transfusiology & Haematology Today / Transfuze a Hematologie Dnes, 2013, Vol 19, Issue 1, p8
- ISSN
1213-5763
- Publication type
Academic Journal