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siRNA-mediated AML1/MTG8 depletion affects differentiation and proliferation-associated gene expression in t(8;21)-positive cell lines and primary AML blasts
- Source :
- Oncogene. 25:6067-6078
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- The chromosomal translocation t(8;21) is associated with 10-15% of all cases of acute myeloid leukaemia (AML). The resultant fusion protein AML1/MTG8 interferes with haematopoietic gene expression and is an important regulator of leukaemogenesis. We studied the effects of small interfering RNA (siRNA)-mediated AML1/MTG8 depletion on global gene expression in t(8;21)-positive leukaemic cell lines and in primary AML blasts using cDNA arrays, oligonucleotide arrays and real-time reverse transcription-polymerase chain reaction (RT-PCR). Suppression of AML1/MTG8 results in the increased expression of genes associated with myeloid differentiation, such as AZU1, BPI, CTSG, LYZ and RNASE2 as well as of antiproliferative genes such as IGFBP7, MS4A3 and SLA both in blasts and in cell lines. Furthermore, expression levels of several genes affiliated with drug resistance or indicative of poor prognosis AML (BAALC, CD34, PRG2, TSPAN7) are affected by AML1/MTG8 depletion. In conclusion, siRNA-mediated suppression of AML1/MTG8 cause very similar changes in gene expression pattern in t(8;21)-positive cell lines and in primary AML blasts. Furthermore, the results suggest that the specific targeting of AML1/MTG8 function may be a promising approach for complementing existing treatment strategies.
- Subjects :
- Male
Cancer Research
Small interfering RNA
Chromosomes, Human, Pair 21
Cellular differentiation
Biology
Translocation, Genetic
RUNX1 Translocation Partner 1 Protein
Cell Line, Tumor
Proto-Oncogene Proteins
hemic and lymphatic diseases
Gene expression
Genetics
Humans
Gene silencing
RNA, Small Interfering
neoplasms
Molecular Biology
BAALC
Cell Proliferation
DNA Primers
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Cell Differentiation
Middle Aged
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Gene expression profiling
Haematopoiesis
Leukemia, Myeloid
Acute Disease
Core Binding Factor Alpha 2 Subunit
Immunology
Cancer research
Chromosomes, Human, Pair 8
Transcription Factors
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....c022e0febd126e64a8f914de4af97c2e