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

Journal of Experimental & Clinical Cancer Research

Luis F Jave-Suárez³  Alejandro Bravo-Cuellar³  Esperanza Barrera-Chaires²  Óscar González-Ramella⁴  Ruth de Celis³  José M Lerma-Díaz³  Pablo C Ortiz-Lazareno³  Georgina Hernández-Flores³  Carmen Gurrola-Díaz¹  Adriana Aguilar-Lemarroy³  Jorge Torres-Flores³  Judith A Rosales-Aviña³ 

[1] Instituto de Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 900, CP 44340, Guadalajara, Jalisco, Mexico;Servicio de Hematología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Hospital No. 278, CP 44280, Guadalajara, Jalisco, Mexico;División de Inmunología, Centro de Investigación Biomédica de Occidente - IMSS, Sierra Mojada No. 800, CP 44340, Guadalajara, Jalisco, Mexico;Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, CP 44340, Guadalajara, Jalisco, Mexico

关键词: Apoptosis;    PBX;    PREP1;    MEIS1;    leukemia;    TALE genes;   

Others  :  827017
DOI  :  10.1186/1756-9966-30-112

 received in 2011-09-14, accepted in 2011-12-20,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Rosales-Aviña et al; licensee BioMed Central Ltd.

【 图 表 】

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