| Title |
BCL2A1a Over-Expression in Murine Hematopoietic Stem and Progenitor Cells Decreases Apoptosis and Results in Hematopoietic Transformation
|
|---|---|
| Published in |
PLOS ONE, October 2012
|
| DOI | 10.1371/journal.pone.0048267 |
| Pubmed ID | |
| Authors |
Jean-Yves Métais, Thomas Winkler, Julia T. Geyer, Rodrigo T. Calado, Peter D. Aplan, Michael A. Eckhaus, Cynthia E. Dunbar |
| Abstract |
We previously reported the development of a lethal myeloid sarcoma in a non-human primate model utilizing retroviral vectors to genetically modify hematopoietic stem and progenitor cells. This leukemia was characterized by insertion of the vector provirus into the BCL2A1 gene, with resultant BCL2A1 over-expression. There is little information on the role of this anti-apoptotic member of the BCL2 family in hematopoiesis or leukemia induction. Therefore we studied the impact of Bcl2a1a lentiviral over-expression on murine hematopoietic stem and progenitor cells. We demonstrated the anti-apoptotic function of this protein in hematopoietic cells, but did not detect any impact of Bcl2a1a on in vitro cell growth or cell cycle kinetics. In vivo, we showed a higher propensity of HSCs over-expressing Bcl2a1a to engraft and contribute to hematopoiesis. Mice over-expressing Bcl2a1a in the hematologic compartment eventually developed an aggressive malignant disease characterized as a leukemia/lymphoma of B-cell origin. Secondary transplants carried out to investigate the primitive origin of the disease revealed the leukemia was transplantable. Thus, Bcl2a1 should be considered as a proto-oncogene with a potential role in both lymphoid and myeloid leukemogenesis, and a concerning site for insertional activation by integrating retroviral vectors utilized in hematopoietic stem cell gene therapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 4% |
| Colombia | 1 | 4% |
| Canada | 1 | 4% |
| Unknown | 24 | 89% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 30% |
| Student > Ph. D. Student | 5 | 19% |
| Student > Master | 5 | 19% |
| Student > Postgraduate | 2 | 7% |
| Professor > Associate Professor | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 5 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 9 | 33% |
| Agricultural and Biological Sciences | 8 | 30% |
| Immunology and Microbiology | 2 | 7% |
| Nursing and Health Professions | 1 | 4% |
| Medicine and Dentistry | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 6 | 22% |