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Two distinct proteins appear to control the switch from fetal to adult globin, based on studies performed in a humanized mouse model and human cells. The findings suggest therapies that target both proteins might induce a fetal-type globin state, which could prove therapeutically useful in individuals with human hemoglobinopathies such as sickle cell disease and thalassemia.
The leukemia/lymphoma-related factor (LRF) and B-cell lymphoma/leukemia 11A (BCL11A) are independently involved in the switch, and blocking their production may turn on fetal globin expression, Takeshi Masuda, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues report (SCIENCE. 2015 Jan 15;351[6270]:285-9)
Using a humanized mouse model, the researchers knocked out the ZBTB7A gene, which is responsible for producing LRF. This action boosted the expression of genes that control fetal but not adult-type hemoglobin. Knocking out the gene in human cells also resulted in an increase in fetal hemoglobin proteins.
The researchers then examined BCL11A, which is involved with fetal hemoglobin but does not suppress it. When genes were knocked out for both ZBTB7A and BCL11A in the mice, fetal hemoglobin represented a 91%-94% greater percentage of total hemoglobin than when either gene alone was knocked out.
The research was supported by awards and/or grants from the National Institute of Diabetes and Digestive and Kidney Disease, the Doris Duke Charitable Foundation, the National Institutes of Health, and the American Society of Hematology. Dr. Masuda, along with two other study authors, is a contributor to a patent application filed on behalf of Brigham and Women’s Hospital related to therapeutic targeting of the pathways.
Click here to read the study at Science.
Two distinct proteins appear to control the switch from fetal to adult globin, based on studies performed in a humanized mouse model and human cells. The findings suggest therapies that target both proteins might induce a fetal-type globin state, which could prove therapeutically useful in individuals with human hemoglobinopathies such as sickle cell disease and thalassemia.
The leukemia/lymphoma-related factor (LRF) and B-cell lymphoma/leukemia 11A (BCL11A) are independently involved in the switch, and blocking their production may turn on fetal globin expression, Takeshi Masuda, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues report (SCIENCE. 2015 Jan 15;351[6270]:285-9)
Using a humanized mouse model, the researchers knocked out the ZBTB7A gene, which is responsible for producing LRF. This action boosted the expression of genes that control fetal but not adult-type hemoglobin. Knocking out the gene in human cells also resulted in an increase in fetal hemoglobin proteins.
The researchers then examined BCL11A, which is involved with fetal hemoglobin but does not suppress it. When genes were knocked out for both ZBTB7A and BCL11A in the mice, fetal hemoglobin represented a 91%-94% greater percentage of total hemoglobin than when either gene alone was knocked out.
The research was supported by awards and/or grants from the National Institute of Diabetes and Digestive and Kidney Disease, the Doris Duke Charitable Foundation, the National Institutes of Health, and the American Society of Hematology. Dr. Masuda, along with two other study authors, is a contributor to a patent application filed on behalf of Brigham and Women’s Hospital related to therapeutic targeting of the pathways.
Click here to read the study at Science.
Two distinct proteins appear to control the switch from fetal to adult globin, based on studies performed in a humanized mouse model and human cells. The findings suggest therapies that target both proteins might induce a fetal-type globin state, which could prove therapeutically useful in individuals with human hemoglobinopathies such as sickle cell disease and thalassemia.
The leukemia/lymphoma-related factor (LRF) and B-cell lymphoma/leukemia 11A (BCL11A) are independently involved in the switch, and blocking their production may turn on fetal globin expression, Takeshi Masuda, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and his colleagues report (SCIENCE. 2015 Jan 15;351[6270]:285-9)
Using a humanized mouse model, the researchers knocked out the ZBTB7A gene, which is responsible for producing LRF. This action boosted the expression of genes that control fetal but not adult-type hemoglobin. Knocking out the gene in human cells also resulted in an increase in fetal hemoglobin proteins.
The researchers then examined BCL11A, which is involved with fetal hemoglobin but does not suppress it. When genes were knocked out for both ZBTB7A and BCL11A in the mice, fetal hemoglobin represented a 91%-94% greater percentage of total hemoglobin than when either gene alone was knocked out.
The research was supported by awards and/or grants from the National Institute of Diabetes and Digestive and Kidney Disease, the Doris Duke Charitable Foundation, the National Institutes of Health, and the American Society of Hematology. Dr. Masuda, along with two other study authors, is a contributor to a patent application filed on behalf of Brigham and Women’s Hospital related to therapeutic targeting of the pathways.
Click here to read the study at Science.
FROM SCIENCE