학술논문

MEIS1, PREP1, and PBX4 Are Differentially Expressed in Acute Lymphoblastic Leukemia: Association of MEIS1 Expression with Higher Proliferation and Chemotherapy Resistance
Document Type
article
Source
Journal of Experimental & Clinical Cancer Research, Vol 30, Iss 1, p 112 (2011)
Subject
TALE genes
leukemia
MEIS1
PREP1
PBX
Apoptosis
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1756-9966
Abstract
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.