Open AccessGlobal 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
Author(s) -
AvilésVázquez Sócrates,
ChávezGonzález Antonieta,
HidalgoMiranda Alfredo,
MorenoLorenzana Dafne,
ArriagaPizano Lourdes,
SandovalEsquivel Miguel Á.,
AyalaSánchez Manuel,
Aguilar Rafael,
AlfaroRuiz Luis,
Mayani Hector
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1187
Subject(s) - progenitor cell , stem cell , myeloid leukemia , biology , haematopoiesis , cancer research , myeloid , bone marrow , microbiology and biotechnology , cell cycle , cd34 , hematopoietic stem cell , stromal cell , immunology , cell , genetics
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.