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Ex vivo expansion of normal and chronic myeloid leukemic stem cells without functional alteration using a NUP98HOXA10homeodomain fusion gene
- Source :
- Leukemia
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- HOX genes have been implicated as regulators of normal and leukemic stem cell functionality, but the extent to which these activities are linked is poorly understood. Previous studies revealed that transduction of primitive mouse hematopoietic cells with a NUP98HOXA10homeodomain (NA10HD) fusion gene enables a subsequent rapid and marked expansion in vitro of hematopoietic stem cell numbers without causing their transformation or deregulated expansion in vivo. To determine whether forced expression of NA10HD in primitive human cells would have a similar effect, we compared the number of long-term culture-initiating cells (LTC-ICs) present in cultures of lenti-NA10HD versus control virus-transduced CD34(+) cells originally isolated from human cord blood and chronic phase (CP) chronic myeloid leukemia (CML) patients. We found that NA10HD greatly increases outputs of both normal and Ph(+)/BCR-ABL(+) LTC-ICs, and this effect is particularly pronounced in cultures containing growth factor-producing feeders. Interestingly, NA10HD did not affect the initial cell cycle kinetics of the transduced cells nor their subsequent differentiation. Moreover, immunodeficient mice repopulated with NA10HD-transduced CP-CML cells for more than 8 months showed no evidence of altered behavior. Thus, NA10HD provides a novel tool to enhance both normal and CP-CML stem cell expansion in vitro, without apparently altering other properties.
- Subjects :
- Cancer Research
Oncogene Proteins, Fusion
Cellular differentiation
Fusion Proteins, bcr-abl
Antigens, CD34
Mice, SCID
Mice
0302 clinical medicine
Mice, Inbred NOD
Cells, Cultured
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle
Hematopoietic stem cell
Cell Differentiation
Hematology
Fetal Blood
HOX genes
Cell biology
Endothelial stem cell
Haematopoiesis
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Cord blood
Leukemia, Myeloid, Chronic-Phase
Neoplastic Stem Cells
Original Article
long-term culture-initiating cells
Stem cell
Adult stem cell
Blotting, Western
Transplantation, Heterologous
Biology
Real-Time Polymerase Chain Reaction
Colony-Forming Units Assay
03 medical and health sciences
chronic myeloid leukemia
Cancer stem cell
medicine
Animals
Humans
RNA, Messenger
Cell Proliferation
030304 developmental biology
Homeodomain Proteins
Receptors, Interleukin-2
Hematopoietic Stem Cells
Molecular biology
Nuclear Pore Complex Proteins
Homeobox A10 Proteins
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....8286c37305d72bb13b3cd08a1c0c3bcd