| Abstract | Akutna mijeloična leukemija je maligna bolest karakterizirana klonskom proliferacijom nezrelih aberantnih mijeloidnih stanica (blasta) uz infiltraciju koštane srži koja najčešće prelazi u krv, a ponekad se može proširiti i na druge dijelove tijela, uključujući limfne čvorove, jetru, slezenu, središnji živčani sustava, testise, kožu i sluznice. Svake godine u svijetu oboli 5,4/100 000 ljudi. Klinički se prezentira simptomima pancitopenije s preživljenjem od nekoliko mjeseci nakon postavljanja dijagnoze ukoliko se ne liječi. Jedina terapijska opcija koja omogućuje izliječene je primjena visokih doza citotoksičnih lijekova i susljedna transplantacija krvotvornih matičnih stanica (TKMS) koja zahvaljujući učinku presatka protiv primatelja uništi preostale blaste. Navedena terapija ne može biti primijenjena u svi oboljelih od AML-a najčešće zbog općeg lošeg stanja bolesnika. Leukemijski blasti posjeduju razne mogućnosti prilagodbe pomoću kojih izbjegavaju uništenje od strane imunosnog sustava bolesnika, ali i od donorskih stanica infundiranih bolesniku tijekom TKMS što može dovesti do relapsa bolesti u većine bolesnika. Složena klonska pozadina, mogućnost genske i epigenetske modifikacija te činjenica da je većina antigena izražena na blastima izražena i na zdravim stanicama dovodi do otežanog odabira idealnog ciljnog antigena s kojim bi se moglo djelovati na konačno uništenje malignih stanica. Trenutno se razvijaju brojni terapijski pristupi čiji je temelj imunosna kontrola proliferacije leukemijskih blasta poput primjene monoklonskih protutijela, blokade kontrolnih točaka, stanična terapija stanicama CAR-T i NK te cijepljenje. |
| Abstract (english) | Acute myeloid leukaemia is a malignant disease characterized by clonal proliferation of immature aberrant myeloid cells (blasts) with infiltration of the bone marrow that most often spreads to the blood and sometimes can spread to other parts of the body, including lymph nodes, liver, spleen, central nervous system, testicles, skin, and mucous membranes. The incidence of new AML cases is 5.1/100,000 per year. AML presents with symptoms of pancytopenia and has survival of several months after diagnosis if left untreated. The only therapeutic option that has curative potential is a combination of cytotoxic drugs and the subsequent transplantation of hematopoietic stem cells (HTSC) that destroys the remaining blasts due to graft versus leukaemia effect. Unfortunately, HSCT cannot be used in all patients with AML, most commonly because of the poor general condition of patients. Leukemic blasts possess various adaptation mechanisms that offers them a way to avoid destruction by the patient's immune system, but also by the infused donor cells during HSCT, which leads to relapse in most patients. The complex clonal background, the possibility of genetic and epigenetic modification and the fact that most antigens expressed on blasts are also expressed on healthy cells makes it difficult to choose the ideal target antigen that could be used for the complete destruction of malignant cells. Numerous approaches are currently being developed, the basis of which is immune control of the proliferation of leukemic blasts, such as monoclonal antibodies, checkpoint blockade, CAR-T cells, NK-cells, and vaccination. |
