Intercellular adhesion molecules of acute myeloid leukemia cells and drug resistance phenotype
One of the most important roles in the formation of drug resistance in acute myeloid leukemia (AML) cells plays adhesion to mesenchymal stromal cells and extracellular matrix of the bone marrow. Previously we have shown that the phenotype of drug resistance in AML cells may also occur when activated homotypic cell-cell adhesion in multicellular aggregates. In turn, the suppression of homotypic cell-cell adhesion prevents the formation of drug-resistance phenotype of AML cells. In this work, the identification of AML cell adhesion molecules was performed and the role of identified molecules in the activation of homotypic cell-cell adhesion was studied. In our study we used THP-1 cells (multicellular aggregates forming cells) and KG-1 cells (multicellular aggregates not forming cells). The identification of cell adhesion molecules was performed by flow cytometry with using monoclonal antibodies to human CD11a, CD11b, CD11c, CD18, CD50, CD54 and CD102. To study the role of the identified adhesion molecules in the multicellular aggregates formation AML cells were incubated with appropriate inhibitory antibodies. When intercellular adhesion was induced by PMA and number of newly formed multicellular aggregates was counted. We showed expression of CD11a, CD11c, CD18, CD54 on THP-1 cells. In turn, on the KG-1cell expressed only CD11a and CD18. We also showed that the use of inhibitory antibodies to CD11a and CD18 decreased multicellular aggregate formation by THP-1 cells to 51 ± 6% relative to a control. Use of inhibitory antibodies to CD54 decreased formation of aggregates to 25 ± 4% relative to a control. In turn, the use of inhibitory antibodies to CD11c has no effect on formation of multicellular aggregate by THP-1 cells. Thus, in the formation of multicellular aggregates and drug-resistance phenotype of AML cells may be involved intercellular adhesion molecule CD11a, CD18 and CD54.