Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib

• Published in: Cancer medicine (Malden, MA) MA), 2017-12, Vol.6 (12), p.2942-2956
• Main Authors: Avilés‐Vázquez, Sócrates, Chávez‐González, Antonieta, Hidalgo‐Miranda, Alfredo, Moreno‐Lorenzana, Dafne, Arriaga‐Pizano, Lourdes, Sandoval‐Esquivel, Miguel Á., Ayala‐Sánchez, Manuel, Aguilar, Rafael, Alfaro‐Ruiz, Luis, Mayani, Hector
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Biology; Case-Control Studies; Cell adhesion & migration; Cell Biomarkers; Cell cycle; chronic myeloid leukemia; Computational Biology; Databases, Genetic; Gene expression; gene expression profiles; Gene Expression Profiling - methods; Gene Expression Regulation, Leukemic; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; hematopoietic stem/progenitor cells; Humans; Imatinib; Imatinib Mesylate - pharmacology; Ion Channels - genetics; Ion Channels - metabolism; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Oligonucleotide Array Sequence Analysis; Original Research; Protein Kinase Inhibitors - pharmacology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Peptide - genetics; Receptors, Peptide - metabolism; Targeted cancer therapy; Transcriptome; Tumor Cells, Cultured
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1187

In this study, we determined the gene expression profiles of bone marrow‐derived cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML) patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were closer to that of normal progenitors, whereas normal HSCs showed the most different expression profile of all. We found that the expression profiles of HSCs and HPCs from CML marrow were closer to each other than those of HSCs and HPCs from normal marrow. The major biologic processes dysregulated in CML cells included DNA repair, cell cycle, chromosome condensation, cell adhesion, and the immune response. We also determined the genomic changes in both normal and CML progenitor cells under culture conditions, and found that several genes involved in cell cycle, steroid biosynthesis, and chromosome segregation were upregulated, whereas genes involved in transcription regulation and apoptosis were downregulated. Interestingly, these changes were the same, regardless of the addition of Imatinib (IM) to the culture. Finally, we identified three genes—PIEZO2, RXFP1, and MAMDC2‐ that are preferentially expressed by CML primitive cells and that encode for cell membrane proteins; thus, they could be used as biomarkers for CML stem cells. Gene expression profiles of hematopoietic stem and progenitor cells from CML patients have been obtained. The in vitro effect of Imatinib on such gene expression profiles was assessed. Potential leukemic biomarker genes were identified.