title: MEIS1, PREP1, and PBX4 are differentially expressed in acute lymphoblastic leukemia: association of MEIS1 expression with higher proliferation and chemotherapy resistance.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente - IMSS, Sierra Mojada No. 800, CP 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Rosales-Aviña
authors.forename: Jorge
authors.initials: J
authors.lastname: Torres-Flores
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Lemarroy
authors.forename: Carmen
authors.initials: C
authors.lastname: Gurrola-Díaz
authors.forename: Georgina
authors.initials: G
authors.lastname: Hernández-Flores
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Ortiz-Lazareno
authors.forename: José M
authors.initials: JM
authors.lastname: Lerma-Díaz
authors.forename: Ruth
authors.initials: R
authors.lastname: de Celis
authors.forename: Óscar
authors.initials: Ó
authors.lastname: González-Ramella
authors.forename: Esperanza
authors.initials: E
authors.lastname: Barrera-Chaires
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bravo-Cuellar
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jave-Suárez
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C486618:PBX4 protein, human; C106682:PKNOX1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D005047:Etoposide