EKSPRESIJA mikroRNK (miRNK) U MIJELODISPLASTIČNOM SINDROMU (MDS)

Mirjana Mariana Kardum Paro, Inga Mandac Rogulj, Gordana Kaić, Biljana Jelić Puškarić, Ika Kardum-Skelin, Anita Škrtić, Slobodanka Ostojić Kolonić

Sindrom mijelodisplazije ili mijelodisplastični sindrom (MDS) naziv je za skupinu heterogenih klonskih hematoloških poremećaja hematopoetskih matičnih stanica, praćenih neučinkovitom hematopoezom jedne ili više staničnih linija i pojavom posljedičnih citopenija s povišenim rizikom od progresije u akutnu mijeloičnu leukemiju (AML). Mikroglasničke ribonukleinske kiseline (miRNK; engl. Micro Messenger Ribonucleic Acid – miRNA) kratke su, nekodirajuće molekule RNK koje, osim što pridonose patogenezi MDS-a, djeluju i kao regulatori epigenetičkih mehanizama i potencijalni su prognostički biljezi za ranu dijagnostiku i klasifikaciju MDS-a. Cilj je rada bilo ispitivanje razine promjene genskih ekspresija specifičnih miRNK (hsa-miR-125a, hsa-miR-99b, hsa-miR-126 i hsa-miR-125b) u plazmi zdravih dobrovoljaca i ispitanika s dijagnozom MDS-a. Ispitivanje se provodilo u Kliničkom zavodu za medicinsku biokemiju i laboratorijsku medicinu Kliničke bolnice Merkur, akreditiranome prema normi EN ISO 15189:2012. Genske ekspresije navedenih, specifičnih miRNK određene su u uzorcima plazme zdravih dobrovoljaca (4) i ispitanika s MDS-om (33) kojima je on dijagnosticiran u Zavodu za hematologiju Klinike za unutarnje bolesti Kliničke bolnice Merkur, Referentnom centru Ministarstva zdravlja Republike Hrvatske za dijagnostiku i liječenje MDS-a. Statistički značajne razlike genske ekspresije specifičnih miRNK u zdravih dobrovoljaca u odnosu prema ispitanicima s MDS-om nisu nađene [P (hsa-miR-125a) = 0,398; P (hsa-miR-99b) = 0,134; P (hsa-miR-126) = 0,305; P (hsa-miR-125b) = 0,079], a razina promjene genskih ekspresija miRNK (engl. miRNA ratios) hsa-miR-125a i hsa-miR-99b u ispitanika s MDS-om bila je gotovo dva puta viša u odnosu prema normaliziranim razinama genske ekspresije u zdravih dobrovoljaca (2,30 prema 1,90) i više od dva puta viša od razine promjene genske ekspresije miRNK hsa-miR-125b. Rezultati istraživanja upućuju na to da bi genske ekspresije miRNK hsa-miR-125a i hsa-miR-99b mogle biti regulirane istim mehanizmom i da bi mogle biti klinički važne u ispitanika s MDS-om.

Myelodisplasia or myelodysplastic syndrome (MDS) is the name for a group of heterogeneous clonal hematological disorders of hematopoietic stem cells followed by ineffective hematopoesis of one or more cell lines and the emergence of consequent cytopenias with increased risk of progression to acute myelogenous leukemia (AML). Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding RNA molecules that, apart from contributing to MDS pathogenesis, act as regulators of epigenetic mechanisms and also are recognized as potential prognostic markers for early diagnosis and classification of MDS. The aim of the study was to examine the levels of gene expression of specific miRNAs (hsa-miR-125a, hsa-miR-99b, hsa-miR-126 and hsa-miR-125b) in healthy volunteers plasma and MDS diagnosed patients. Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of four healthy volunteers and 33 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. Statistically significant difference in gene expression of miRNA in healthy volunteers compared to the MDS patients was not found (P [hsa-miR-125a] = 0.398; P [hsa-miR-99b] = 0.134; P [hsa- miR-126] = 0.305; P [hsa-miR-125b] = 0.079). MiRNA ratios of hsa-miR-125a and hsa-miR-99b in MDS patients were almost twice as high compared to normalized levels of gene expression in healthy volunteers (2.30 versus 1.90), and the level of change of miRNAs hsa-miR-125 and hsa-miR-99b was more than two times higher than the level of change of miRNA hsa-miR-125b. Finally, the results of the research indicate that the gene expression of miRNAs hsa-miR-125a and hsa-miR-99b could be regulated by the same mechanism and could be clinically relevant in MDS patients.