Contributions
Abstract: PB1621
Type: Publication Only
Background
Acute leukemia (AL) is a severe disease of the hematopoietic system and associated with a poor outcome for patients. Patient derived xenograft (PDX) mouse models provide an attractive tool to engraft and grow primary tumor cells. In contrast to culture growth, samples can be monitored in a consisting microenvironment. This powerful tool provides the baseline for further experiments like preclinical treatment trials or biology studies. While good engraftment rates were published for primary pediatric ALL samples, engraftment rates of adult ALL samples might be inferior, but remain largely elusive.
Aims
This study aimed to determine engraftment and growing ability of primary adult AL samples in immunodeficient mice. Genetic engineering was performed to evaluate transduction efficiencies by lentiviruses in PDX AL cells.
Methods
Primary adult ALL and AML samples were transplanted into NSG mice in the absence of total body irradiation. Both frozen as well as fresh patient material was used. Human CD45 and human CD38 were stained in blood to monitor successful engraftment. Mice were sacrificed before coming down with leukemia. Isolated cells from bone marrow and spleen were analyzed by flow cytometry. Genetic engineering was performed using lentiviral vector systems and monitored by expression of fluorochrome markers and flow cytometry.
Results
Engraftment and growth was successful in NSG mice in 12 out of 15 primary adult ALL samples. Frozen samples showed a longer median engraftment time with 114.4 days, whereas fresh samples could already be isolated with an average time of 75.29 days. Generally, the engraftment time varied form 47 days up to 166 days and was shortened for slow samples over several passages. Genetic engineering was successfully performed using lentiviral transduction to introduce expression of fluorescent colours for cell marking and monitoring in further experiments.
Conclusion
In summary, we observed a high engraftment rate of primary adult ALL samples in immunodeficient mice which was above what we anticipated from the literature. Adult PDX ALL samples can be transduced with lentiviruses with identical high transduction efficiency as pediatric samples, with an age independent exception of AL PDX cells with BCR-ABL or MLL translocations.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): Translocation, Transduction, Acute lymphoblastic leukemia, acute leukemia
Abstract: PB1621
Type: Publication Only
Background
Acute leukemia (AL) is a severe disease of the hematopoietic system and associated with a poor outcome for patients. Patient derived xenograft (PDX) mouse models provide an attractive tool to engraft and grow primary tumor cells. In contrast to culture growth, samples can be monitored in a consisting microenvironment. This powerful tool provides the baseline for further experiments like preclinical treatment trials or biology studies. While good engraftment rates were published for primary pediatric ALL samples, engraftment rates of adult ALL samples might be inferior, but remain largely elusive.
Aims
This study aimed to determine engraftment and growing ability of primary adult AL samples in immunodeficient mice. Genetic engineering was performed to evaluate transduction efficiencies by lentiviruses in PDX AL cells.
Methods
Primary adult ALL and AML samples were transplanted into NSG mice in the absence of total body irradiation. Both frozen as well as fresh patient material was used. Human CD45 and human CD38 were stained in blood to monitor successful engraftment. Mice were sacrificed before coming down with leukemia. Isolated cells from bone marrow and spleen were analyzed by flow cytometry. Genetic engineering was performed using lentiviral vector systems and monitored by expression of fluorochrome markers and flow cytometry.
Results
Engraftment and growth was successful in NSG mice in 12 out of 15 primary adult ALL samples. Frozen samples showed a longer median engraftment time with 114.4 days, whereas fresh samples could already be isolated with an average time of 75.29 days. Generally, the engraftment time varied form 47 days up to 166 days and was shortened for slow samples over several passages. Genetic engineering was successfully performed using lentiviral transduction to introduce expression of fluorescent colours for cell marking and monitoring in further experiments.
Conclusion
In summary, we observed a high engraftment rate of primary adult ALL samples in immunodeficient mice which was above what we anticipated from the literature. Adult PDX ALL samples can be transduced with lentiviruses with identical high transduction efficiency as pediatric samples, with an age independent exception of AL PDX cells with BCR-ABL or MLL translocations.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): Translocation, Transduction, Acute lymphoblastic leukemia, acute leukemia