PNH is a disease in which a mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. in the gene called PIG-A is acquired in the stem cells stem cells: Cells in the body that develop into other cells. There are two main sources of stem cells. Embryonic stem cells come from human embryos and are used in medical research. Adult stem cells in the body repair and maintain the organ or tissue in which they are found. Blood-forming (hemapoietic) stem… (mother cells of all blood cells) in the bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. of patients. As a result the blood cells produced by this stem cell are defective. While previous discover of the PIG-A gene PIG-A gene: The gene that is in charge of making a protective shield of proteins on normal red blood cells. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a change (mutation) in the PIG-A gene of a single stem cell in the bone marrow. mutation has helped to explain the symptoms in the disease, it remains unclear how PIG-A mutation makes the PNH stem cells outcompete healthy stem cells. In this project we propose to apply a very efficient sequencing technology to examine all genes in PNH stem cells to see whether additional mutations will explain how PNH develops. In the initial experiments we have identified such additional mutations. They may help to devise treatments to eradicate PNH stem cells from the patient’s bone marrow.
Paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) is a blood disease with chronic clinical course. PNH has been considered a genetically simple disease caused by PIG-A gene PIG-A gene: The gene that is in charge of making a protective shield of proteins on normal red blood cells. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a change (mutation) in the PIG-A gene of a single stem cell in the bone marrow. mutations. However, according to our next generation search of whole human gene (in comparison between PNH cells and normal blood cells), various kinds of other genetic abnormalities were clearly found in addition to the acquisition of PIG-A mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. . Moreover, we discovered multiple (2 to 3) PIG-A mutations in the different PNH cells from the same PNH patients. Based on such novel results we are first to elucidate the variations of causes and explain the differences in symptoms of PNH for individual patients. For example, newly identified some genetic abnormalities in this project had been already commonly reported also in myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… , which is more aggressive blood disease. It makes sense since a part of PNH cases show more aggressive clinical conditions than the other PNH patients. In this first-year progress report, we mention novel findings of new genetic abnormality in addition to PIG-A mutations in PNH. Deeper research for discovered genes in more PNH cases will confirm these conclusions for the feedback to better patients’ care in the clinic. More details of this project were presented in 55th American Society of Hematology Annual Meeting @New Orleans, LA.