MEIS1, PREP1, and PBX4 are differentially expressed in acute lymphoblastic leukemia: association of MEIS1 expression with higher proliferation and chemotherapy resistance

• Published in: Journal of experimental & clinical cancer research 2011-12, Vol.30 (1), p.112-112, Article 112
• Main Authors: Rosales-Aviña, Judith A, Torres-Flores, Jorge, Aguilar-Lemarroy, Adriana, Gurrola-Díaz, Carmen, Hernández-Flores, Georgina, Ortiz-Lazareno, Pablo C, Lerma-Díaz, José M, de Celis, Ruth, González-Ramella, Óscar, Barrera-Chaires, Esperanza, Bravo-Cuellar, Alejandro, Jave-Suárez, Luis F
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Apoptosis; Base Sequence; Cell Growth Processes - physiology; Cell Line, Tumor; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Down-Regulation; Drug Resistance, Neoplasm; Etoposide - pharmacology; Flow cytometry; Gene Expression Regulation, Leukemic; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Humans; Jurkat Cells; leukemia; MEIS1; Molecular Sequence Data; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; PBX; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; PREP1; Proteins; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; TALE genes; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcriptional Activation; Up-Regulation
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/1756-9966-30-112

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. 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. Here 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. Our 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.