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Cancer Med. 2017 Dec;6(12):2942-2956. doi: 10.1002/cam4.1187. Epub 2017 Oct 13.

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.

Author information

1
Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security, Mexico City, Mexico.
2
National Institute of Genomic Medicine, Mexico City, Mexico.
3
Immunochemistry Research Unit, National Medical Center, Mexican Institute for Social Security, Mexico City, Mexico.
4
Department of Hematology, La Raza Medical Center, Mexican Institute for Social Security, Mexico City, Mexico.
5
Department of Hip Surgery, Villa Coapa General Hospital, Mexican Institute for Social Security, Mexico City, Mexico.

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 (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.

KEYWORDS:

Cell Biomarkers; Imatinib; chronic myeloid leukemia; gene expression profiles; hematopoietic stem/progenitor cells

PMID:
29030909
PMCID:
PMC5727298
DOI:
10.1002/cam4.1187
[Indexed for MEDLINE]
Free PMC Article

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