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SHR Neuro Cancer Cardio Lipid Metab Microb
Staber, PB; Linkesch, W; Zauner, D; Beham-Schmid, C; Guelly, C; Schauer, S; Sill, H; Hoefler, G.
Common alterations in gene expression and increased proliferation in recurrent acute myeloid leukemia.
Oncogene. 2004; 23(4):894-904
Doi: 10.1038/sj.onc.1207192
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- Leading authors Med Uni Graz
- Höfler Gerald
- Staber Philipp
- Co-authors Med Uni Graz
- Beham-Schmid Christine
- Gülly Christian
- Linkesch Werner
- Schauer Silvia
- Sill Heinz
- Zauner Dorothea
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- Abstract:
- Recurrent disease following high-dose chemotherapy is a major problem in patients with acute myeloid leukemia (AML). To identify its characteristics, we performed expression profiling in blasts from untreated AML and relapse, using a specific cDNA microarray comprising 4128 genes generated by cDNA subtraction supplemented with cancer-associated genes. Expression analysis of 18 AML bone marrow specimens showed that recurrent AML is commonly associated with the mRNA expression changes in a set of 58 genes. Increased cellular proliferation was indicated by the overexpression of the transferrin receptor, proliferating cell nuclear antigen, and G1 cyclins. An immunohistochemical study for Ki-67-positive blasts in 18 paired bone marrow biopsy samples confirmed a highly significant (P<0.0001) increase in the proliferation fraction at relapse. In addition, we found enhanced activation of the RAF/MEK/ERK cascade as mRNAs of MKP-1, c-jun, c-fos, and egr-1 were significantly increased at relapse. Immunohistochemistry and immunoblotting analyses for biphosphorylated ERK1/2 protein provide additional evidence for enhanced activation of the RAF/MEK/ERK pathway. The degree of increase is significantly correlated with the increased proliferation. Furthermore, the genes identified provide a rationale for further studies on predictive diagnosis and therapeutic intervention.
- Find related publications in this database (using NLM MeSH Indexing)
- Acute Disease -
- Adult -
- Aged -
- Blotting, Western -
- Cell Division -
- DNA, Complementary -
- Gene Expression -
- Humans -
- Immunohistochemistry -
- Leukemia, Myeloid - enzymology Leukemia, Myeloid - genetics Leukemia, Myeloid - pathology
- Middle Aged -
- Mitogen-Activated Protein Kinases - metabolism
- Oligonucleotide Array Sequence Analysis -
- Recurrence -
- Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
- AML
- relapse
- proliferation
- RAF/MEK/ERK
- c-DNA subtraction
- c-DNA microarray