Zbornik - Društvo genetičara Srbije

V-Usm-14 ZBORNIK ABSTRAKATA III KONGRESA GENETIÈARA SRBIJE 197
Subotica, 30. novembar - 4. decembar 2004.
DETEKCIJA MINIMALNE REZIDUALNE BOLESTI KOD BOLESNIKA SA
HRONIÈNOM MIJELOIDNOM LEUKEMIJOM (CML) LEÈENIH IMATINIB
MESYLATOM
Anka Radoviæ, Biljana Todoriæ-ivanoviæ, Milica Strnad, Dragana Stamatoviæ,
Koviljka Krtolica 1 i Z. Magiæ 1
Vojnomedicinska Akademija, Beograd
1
Institut za nuklearne nauke «Vinèa», Beograd
Detekcija i praæenje minimalne rezidualne bolesti (MRB), zaostalih malignih æelija
nakon terapije, postalo je jedno od najvanijih zadataka kad su u pitanju bolesnici sa
CML leèeni imatinib mesylatom. Postizanje kompletne hematološke i citogenetske
remisije kod odreðenog broja bolesnika sa CML a zatim relaps bolesti objašnjavaju se
upravo postojanjem malog broja malignih æelija rezistentnih na primenjenu terapiju.
Zbog toga njihovo otkrivanje daje vanu informaciju o efektu terapije kao i moguænost
da terapeut pravovremeno odreaguje pre nego što doðe do relapsa bolesti. RT-PCR
tehnika se pokazala kao najsenzitivnija, omoguæujuæi detekciju jedne maligne æelije na
10 5-106normalnih. Kao pozitivni marker za detekciju MRB koristi se BCR-ABL fuzioni
gen koji ima kljuènu ulogu u patogenezi CML. Detekcija prisustva minimalne rezidualne
bolesti bolesnika sa CML koji su postigli kompletan citogenetski odgovor (0% æelija sa
Philadelfija hromozomom) nakon primenjene terapije imatinib mesylatom. Prisustvo
rezidualnih æelija koje eksprimiraju BCR-ABL himerni gen analizirano je u uzorcima
periferne krvi kod pet bolesnika (od dvadeset na imatinib terapiji) koji su postigli
kompletan citogenetski odgovor. Detekcija je vršena RT-PCR i «nested» RT-PCR
tehnikom. Kod tri bolesnika RT-PCR tehnikom detektovano je prisustvo rearanmana
b3a2 tipa. Kod dva bolesnika je po dobijanju negativnog rezultata nakon RT-PCR
tehnike primenjena «nested» RT-PCRmetoda.
Ovom metodom utvrðeno je prisustvo BCR-ABL rearanmana i to kod jednog bolesnika
b3a2 tip a kod drugog b2a2 tip.
DETECTION OF MINIMAL RESIDUAL DISEASE IN PATIENTS WITH
CHRONIC MYELOGENOUS LEUKEMIA (CML) TREATED WITH
IMATINIB MESYLATE
Detection and monitoring of minimal residual disease (MRD), malignant cells remained
after the therapy, has become one of the most important tasks when it comes to CML patients
treated with imatinib mesylate. The fact that certain number of patients suffering
from CML first achieve complete hematologic and cytogenetic remission which is afterwards
followed by relapse of disease could actually be clarified through the existence of
small number of malignant cells that are resistant to the applied therapy. Therefore, detection
of these cells will provide important information on the effect of therapy as well as offer
a therapist an opportunity to react promptly before the relapse of disease takes place.
RT-PCR technique proved to be the most sensitive one enabling the detection of one malignant
cell in 10 5 -10 6 normal ones. BCR-ABL fusion gene that has a crucial role in
pathogenesis of CML is used as positive marker for detection of MRD. Detection of the
presence of minimal residual disease in CML patients who after the application of imatinib
mesylate therapy reached complete cytogenetic response (0%cells with Philadelphia chromosome).
Presence of residual cells that express BCR-ABL chimerical gene was analysed
in the samples of peripheral blood from five patients (out of twenty undergoing imatinib
therapy) who had reached complete cytogenetic response. Detection was performed by the
means of RT-PCR and nested RT-PCR technique. In three patients b3a2 rearrangement
type was detected by RT-PCR tehnique. In two remaining patients after negative RT-PCR
results nested RT-PCR was applied. By this method BCR-ABL rearrangement was detected
in both patients, one of them having b3a2 type and the other b2a2 type.