Jurkat, CEM, and K562 cells were treated with 170 μM etoposide; t

Jurkat, CEM, and K562 cells were treated with 170 μM etoposide; the ABT-263 cell line percentage of apoptotic cells was measured using Annexin-V-FLUOS. The bars represent means ± Standard deviations (SD) of three independent experiments. C) MEIS1-silenced (LVX-E9 and -E13) cells were treated with 170 μM etoposide for 12 and 24 hours. Parental cells (Jurkat and K562) or empty vector-silenced cells (LVX) were also used. After etoposide treatment WST-1 was added to cell cultures and incubate for 3 additional hours.

The percentage of cell survival was calculated measuring Optical density (OD) at 450 nm (OD of untreated cells was set as 100%). Statistical differences were calculated at the end point of the curves using 2 way ANOVA analysis and Bonferroni posttest, (*) significances are shown between groups only when p ≤ 0.05. Given that K562 cells show a chemotherapeutic-resistant phenotype and that response of these cells to etoposide exposure is the down-modulation of MEIS1, and because AZD2014 we observed that Jurkat cells increased MEIS1 expression and were the most sensitive cells, we postulate that MEIS1 down-regulation could be a mechanism for resistance to etoposide-induced apoptosis. In this regard, Jurkat clones with MEIS1-silenced should be more

resistant than Jurkat infected with the empty virus (pLVX) or with parental Jurkat cells. We tested this hypothesis

exposing the cells to etoposide and measuring the percentage of surviving cells (Figure 6C). From this approach, we observed that Jurkat clones in which MEIS1 was silenced demonstrated a higher percentage of cell survival compared with pLVX infected cells or parental cells. MEIS1 silencing in K562 cells did not further increased the percentage of surviving cells. Discussion TALE genes are a particular group of homeobox genes that are important in the regulation of proliferation, apoptosis, and normal cell differentiation. Anomalous Benzatropine expression of these genes has been involved in the development of hematological malignancies [23]. In this work, we first analyzed variations in the expression of TALE genes in leukemia-derived cell lines compared with normal control cells. In that we observed dissimilar MEIS1, MEIS2, and PREP1 expression levels, we wished to confirm whether these changes were also observed in samples of patients with leukemia. Interestingly, we found variations in MEIS1, PREP1, and PBX4 expression. It has been reported that over-expression of MEIS1 blocks myeloid cell differentiation; thus, high levels of MEIS1 are required to maintain hematopoietic cells in an undifferentiated state [13].

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