Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia
Vladan P Čokić1, Slavko Mojsilović1, Aleksandra Jauković1
1Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
Insights
Chronic myeloid leukemia (CML) involves altered gene expression in CD34(+) cells and granulocytes, driven by the BCR-ABL oncogene. This impacts cell cycle and proliferation signaling pathways, offering therapeutic targets.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- Chronic myeloid leukemia (CML) is characterized by the BCR-ABL fusion gene.
- Understanding gene expression changes in CML is crucial for targeted therapies.
Purpose of the Study:
- To compare gene expression profiles in CD34(+) cells and granulocytes from CML patients.
- To identify signaling pathways affected by the BCR-ABL oncogene in CML.
Main Methods:
- Microarray analysis of peripheral blood CD34(+) cells and granulocytes.
- Comparison between 7 CML patients in chronic phase and 7 healthy donors.
Main Results:
- Gene expression profiles were more pronounced in CML CD34(+) cells (3553 genes) than granulocytes (2701 genes).
- BCR-ABL oncogene upregulated PI3K/AKT and MAPK signaling pathways in CD34(+) cells.
- Specific genes like FOS and STAT1 showed decreased expression, potentially related to Imatinib inhibition.
Conclusions:
- The BCR-ABL fusion gene significantly alters gene expression related to cell cycle, proliferation, and apoptosis in CD34(+) cells.
- Key modifications in PI3K/AKT and MAPK signaling pathways were identified in CML subjects.
Purpose:
We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene.
Methods:
The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012±SD of CD34(+)cells/microl in peripheral blood.
Results:
The gene expression profile was more prominent in CML CD34(+) cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34(+) cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34(+) cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML.
Conclusion:
The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34(+) cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects.
