Abstract
BackgroundThe Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators. In this work, we determined the expression levels of TALE genes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors.ResultsHere we show increased expression of MEIS1, MEIS2, and PREP1 genes in leukemia-derived cell lines compared with blood normal cells. High levels of MEIS1 and PREP1, and low levels of PBX4 expression were also founded in samples of patients with ALL. Importantly, silencing of MEIS1 decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment. Etoposide-induced apoptosis induces down-regulation of MEIS1 expression or PREP1 up-regulation in chemotherapy-resistant cells.ConclusionsOur results indicate that up-regulation of MEIS1 is important for sustaining proliferation of leukemic cells and that down-regulation of MEIS1 or up-regulation of PREP1 and PBX genes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis.
Highlights
The Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators
Higher Expression Levels of MEIS1, MEIS2, and PREP1 Genes in Leukemia-derived Cell Lines Compared with Normal Cells TALE genes are normally involved in the differentiation of hematopoietic cells and their expression has been related with deregulated differentiation
In order to analyze the expression of TALE genes, we first selected primer pairs to amplify these genes and proved these primers by conventional PCR reactions utilizing a pull of complementary DNA obtained from leukemia-derived cell lines (Table 1)
Summary
The Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators. We determined the expression levels of TALE genes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors. TALE proteins include subfamilies MEINOX and PBC. The PBC subfamily contains PBX1, PBX2, PBX3, and PBX4 proteins [3,4]. Expression of TALE genes response to some cytokines, favoring self-renewal or differentiation. In the murine myeloid cell line 32Dcl, it has been observed that MEIS1 can block granulocytic differentiation in response to G-CSF [13]. MEIS1 has been found over-expressed in human leukemic cells [14]
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