Gene expression profiling of CD34(+) cells from patients with myeloproliferative neoplasms
| Autor: | Srinag Bangalore Suresh, Sweta Srivastava, Cecil Ross, Mugdha Sharma, Chandra Bhavani, John Paul, Lokendra Yadav |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Homeobox protein NANOG Cancer Research myeloproliferative neoplasm MYB Biology Chromatin remodeling 03 medical and health sciences 0302 clinical medicine medicine Epigenetics Myeloproliferative neoplasm Cyclin-dependent kinase 1 epigenetics Articles medicine.disease Cell Cycle Gene Molecular biology JAK Chromatin Gene expression profiling 030104 developmental biology Oncology 030220 oncology & carcinogenesis chromatin cell cycle CD34 microarray |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| DOI: | 10.3892/ol.2021.12465 |
| Popis: | Myeloproliferative neoplasms (MPN) are clonal disorders characterized by the increased proliferation of hematopoietic stem cell precursors and mature blood cells. Mutations of Janus kinase 2 (JAK2), Calreticulin (CALR) and MPL (myeloproliferative leukemia virus) are key driver mutations in MPN. However, the molecular profile of triple negative MPN has been a subject of ambiguity over the past few years. Mutations of, methylcytosine dioxygenase TET2, polycomb group protein ASXL1 and histone-lysine N-methyltransferase EZH2 genes have accounted for certain subsets of triple negative MPNs but the driving cause for majority of cases is still unexplored. The present study performed a microarray-based transcriptomic profile analysis of bone marrow-derived CD34(+) cells from seven MPN samples. A total of 21,448 gene signatures were obtained, which were further filtered into 472 upregulated and 202 downregulated genes. Gene ontology and protein-protein interaction (PPI) network analysis highlighted an upregulation of genes involved in cell cycle and chromatin modification in JAK2V617F negative vs. positive MPN samples. Out of the upregulated genes, seven were associated with the hematopoietic stem cell signature, while forty-seven were associated with the embryonic stem cell signature. The majority of the genes identified were under the control of NANOG and E2F4 transcription factors. The PPI network indicated a strong interaction between chromatin modifiers and cell cycle genes, such as histone-lysine N-methyltransferase SUV39H1, SWI/SNF complex subunit SMARCC2, SMARCE2, chromatin remodeling complex subunit SS18, tubulin β (TUBB) and cyclin dependent kinase CDK1. Among the upregulated epigenetic markers, there was a ~10-fold increase in MYB expression in JAK2V617F negative samples. A significant increase in total CD34 counts in JAK2V617F negative vs. positive samples (P |
| Databáze: | OpenAIRE |
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