Výzkum V-D-J rekombinace 1) jako markeru leukémie při sledování reziduální nemoci (MRN) u dětí s akutní lymfoblastickou leukémií (ALL) před transplantací krvetvorných buněk 2) detekce fyziologicky vznikajících cirkulárních produktů V-D-J rekombinace pomocí technik odvozených ze studia MRN u ALL.
V-D-J recombination generates diversity of immunoglobulin (Ig) and T-cell (TCR) receptor genes using assembly of various gene segments. We want to study two aspects of V-D-J recombination: The first aspect includes clonal Ig and TCR rearrangements created as a consequence of malignant hit in the developing lymphocyte. The detection of such clonal rearrangements could improve the clinical management of acute lymphoblastic leukemia (ALL). Using Ig/TCR-based detection of minimal residual disease (MRD), we want to monitor MRD in children undergoing stem cell transplantation (SCT). We aim at achieving MRD-negativity before the transplant using MRD-based therapy adjustment, assuming that MRD-negativity before SCT will substantially improve the outcome of this very high risk group of patients.The second part of the project aims at the physiological V-D-J recombination studied by techniques derived from MRD detection in ALL. We want to introduce a so far unpublished detection of circular excision products (CEP), emerging as %22by-products%22 of immunoglobulin recombination. CEP detection could resolve controversial questions concerning the order of gene segments rearrangements, allelic exclusion and receptor editing in peripheral blood. (en)