**Author details**

identified as marker of chemosensitivity [75, 102]. The main function of this miRNA is activation of apoptotic activity in cells and inducing sensitivity of leukemic to native immunity action. Direct targets for this miRNA are KRAS, NRAS, transcription factor Prospero homebox protein 1 (Prox1) and HMGB1, a member of the high-mobility group box DNA-binding proteins. The CD4 co-receptor is another target for miRNA-181a. Anti-proliferative effect of miRNA-181a is associated with targeting of FBJ murine osteosarcoma viral oncogene homolog (FOS), which is involved in Moloney murine sarcoma viral oncogene homolog (MOS)/ dual specificity mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase (ERK) pathway [76, 103]. miRNA-181a can sensitize leukemic cells to natural killer (NK) cell action [77, 104]. miRNA-181a regulates mechanisms of cell proliferation, differentiation and apoptosis of normal cells. All regulated targets for miRNA-181a are aberrantly expressed and are frequently mutated in acute myeloid leukemia. Promotion of high expression of miRNA-181 in the case of AML may have partial positive effect for chemosensitivity of leukemic cells

Other miRNA, which enhances chemosensitivity of leukemic cells is miRNA-217. This sncRNA decreases leukemic cell proliferation via the cell apoptosis pathway. It targets KRAS regulator of signaling links from extracellular space to the nucleus. KRAS connects multiple

miRNA-155 is oncogenic miRNA, whose high expression is able increase chemoresistant effects of anti-leukemic drugs. Its increased expression is correlated with decreased CR rates and a shorter overall survival (OS) of patients with AML. In our laboratory, primary in vitro leukemic cells were transformed into megakaryocytes after using complexes of polymer car-

Another miRNA from the second group is miRNA-126. High expression of this miRNA correlated with decreased CR rates and shortened OS. Treatment with nanoparticle-based antagonist of miRNA-126 results in strong anti-leukemic effects in murine leukemia models and

Recently determined miRNAs predict the prognosis of AML. From the amount of miRNAs were indicated miRNAs, which expression is dysregulated in patients with poor prognosis of AML. miRNA-107, miRNA-155, miRNA-25, miRNA-29b and miRNA-196a are associated with short OS of patients. The worse prognostic marker was miRNA-25 expression dysregu-

The normal bone marrow stressor or injury factors act as dysregulators of epigenetic and genetic program of hematopoietic stem cells, which is due to downregulation of separated sncRNAs and upregulation of other sncRNAs. These events result in the development of imbalance of regulating cell program and consequent transformation of normal hematopoietic cells into leukemic. In this case, genotypic and phenotypic markers of pathologic cells

and for anti-leukemic activity [78, 79, 105, 106].

rier with antgo-miRNA-155 [80, 107].

lation [76].

94 Myeloid Leukemia

**3. Conclusion**

upstream signals to various downstream signaling pathways [97].

chemo-sensitizing effects of cytarabine and idarubicin in AML cell lines.

Oxana V. Klimenko

Address all correspondence to: o\_klimenko@hotmail.com

SID ALEX GROUP, Ltd. Prague, Czechia
