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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

2017; Wiley; Volume: 6; Issue: 12 Linguagem: Inglês

10.1002/cam4.1187

2045-7634

Sócrates Avilés‐Vázquez, Antonieta Chávez‐González, Alfredo Hidalgo‐Miranda, Dafné Moreno-Lorenzana, Lourdes Arriaga‐Pizano, Miguel Angel Sandoval-Esquivel, Manuel Ayala‐Sánchez, R Jauregui Aguilar, Luis Alfaro-Ruíz, Héctor Mayani,

Chronic Lymphocytic Leukemia Research

Abstract 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 ( HSC s) and progenitor ( HPC s) cells. Our results indicate that the profiles of CML HSC s and HPC s were closer to that of normal progenitors, whereas normal HSC s showed the most different expression profile of all. We found that the expression profiles of HSC s and HPC s from CML marrow were closer to each other than those of HSC s and HPC s 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— PIEZO 2, RXFP 1, and MAMDC 2‐ 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.