MEIS1, PREP1, and PBX4 Are Differentially Expressed in Acute Lymphoblastic Leukemia: Association of MEIS1 Expression with Higher Proliferation and Chemotherapy Resistance

<p>Abstract</p> <p>Background</p> <p>The Three-amino acid-loop-extension (<it>TALE</it>) 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 <it>TALE </it>genes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors.</p> <p>Results</p> <p>Here we show increased expression of <it>MEIS1, MEIS2, </it>and <it>PREP1 </it>genes in leukemia-derived cell lines compared with blood normal cells. High levels of <it>MEIS1 </it>and <it>PREP1</it>, and low levels of <it>PBX4 </it>expression were also founded in samples of patients with ALL. Importantly, silencing of <it>MEIS1 </it>decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment. Etoposide-induced apoptosis induces down-regulation of MEIS1 expression or <it>PREP1 </it>up-regulation in chemotherapy-resistant cells.</p> <p>Conclusions</p> <p>Our results indicate that up-regulation of <it>MEIS1 </it>is important for sustaining proliferation of leukemic cells and that down-regulation of <it>MEIS1 </it>or up-regulation of <it>PREP1 </it>and <it>PBX </it>genes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis.</p