CHARACTERIZATION OF HEMATOPOIETIC SAMPLES FROM PYRUVATE KINASE DEFICIENCY PATIENTS
(Abstract release date: 05/18/17)
EHA Library. Sanchez-Dominguez R. 05/18/17; 182553; PB1839
Rebeca Sanchez-Dominguez
Contributions
Contributions
Abstract
Abstract: PB1839
Type: Publication Only
Background
Pyruvate Kinase Deficiency (PKD) is an autosomal recessive disease caused by mutations in the PKLR gene. PKD produces chronic non-spherocytic hemolytic anemia, which can be fatal during early childhood and may result in lifelong transfusion dependence that in some instances persists despite therapeutic splenectomy. Although not considered a standard-of-care, allogeneic bone marrow transplantation has been curative in a limited number of cases. These findings, and the evidence that PKLR gene mutations are likely the sole etiology of the disorder, make PKD a candidate for gene therapy. Our lab has developed a therapeutic Orphan Drug lentiviral product (EMA: EU/3/14/1330; FDA: DRU-2016-5168) for the treatment of PKD and is working to develop an efficient and safe gene therapy clinical trial for the treatment of PKD.
Aims
In order to improve this new treatment, a more deep knowledge of the disease and its associated pathophysiology is necessary.
Methods
To characterize the hematopoietic profile of this disease, we have standardized flow cytometry protocols to perform both a qualitative and quantitative study of different population subsets. These included subsets of the hematopoietic stem cell compartment, erythroid progenitors, reticulocytes, mature erythrocytes and other mature lineages. Human routine samples consisted of peripheral blood, bone marrow and cord blood from PKD patients. In addition, xenogenic engraftment studies in immnunodeficient (NSG) mice were also performed.
Results
Flow cytometry studies showed a clear imbalance in the erythroid populations. On the other hand, human PKD progenitors were able to engraft into NSG mice demonstrating that the disease does not likely impair hematopoietic stem cell capabilities.
Conclusion
Pyruvate Kinase Deficiency (PKD) is an autosomal recessive disease caused by mutations in the PKLR gene. Our lab has recently developed a therapeutic Orphan Drug lentiviral product for the treatment of PKD. In order to improve this new treatment, we are also working to deep into the knowledge of the disease and its associated pathophysiology. Flow cytometry studies have shown a clear imbalance in the erythroid populations. Functionally, results in NSG mice we have demonstrated that the disease does not likely impair hematopoietic stem cell capabilities.
Session topic: 27. Enzymopathies, membranopathies and other anemias
Abstract: PB1839
Type: Publication Only
Background
Pyruvate Kinase Deficiency (PKD) is an autosomal recessive disease caused by mutations in the PKLR gene. PKD produces chronic non-spherocytic hemolytic anemia, which can be fatal during early childhood and may result in lifelong transfusion dependence that in some instances persists despite therapeutic splenectomy. Although not considered a standard-of-care, allogeneic bone marrow transplantation has been curative in a limited number of cases. These findings, and the evidence that PKLR gene mutations are likely the sole etiology of the disorder, make PKD a candidate for gene therapy. Our lab has developed a therapeutic Orphan Drug lentiviral product (EMA: EU/3/14/1330; FDA: DRU-2016-5168) for the treatment of PKD and is working to develop an efficient and safe gene therapy clinical trial for the treatment of PKD.
Aims
In order to improve this new treatment, a more deep knowledge of the disease and its associated pathophysiology is necessary.
Methods
To characterize the hematopoietic profile of this disease, we have standardized flow cytometry protocols to perform both a qualitative and quantitative study of different population subsets. These included subsets of the hematopoietic stem cell compartment, erythroid progenitors, reticulocytes, mature erythrocytes and other mature lineages. Human routine samples consisted of peripheral blood, bone marrow and cord blood from PKD patients. In addition, xenogenic engraftment studies in immnunodeficient (NSG) mice were also performed.
Results
Flow cytometry studies showed a clear imbalance in the erythroid populations. On the other hand, human PKD progenitors were able to engraft into NSG mice demonstrating that the disease does not likely impair hematopoietic stem cell capabilities.
Conclusion
Pyruvate Kinase Deficiency (PKD) is an autosomal recessive disease caused by mutations in the PKLR gene. Our lab has recently developed a therapeutic Orphan Drug lentiviral product for the treatment of PKD. In order to improve this new treatment, we are also working to deep into the knowledge of the disease and its associated pathophysiology. Flow cytometry studies have shown a clear imbalance in the erythroid populations. Functionally, results in NSG mice we have demonstrated that the disease does not likely impair hematopoietic stem cell capabilities.
Session topic: 27. Enzymopathies, membranopathies and other anemias
{{ help_message }}
{{filter}}