Basics of Blood Disorders
Blood is the carrier of a multitude of fundamental body processes—responsible for delivering vital nutrients/oxygen and for removing wastes. Like the highway exchange feeding a city of life, blood is simply essential. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of blood related diseases is known as hematology.
This single therapeutic area covers a broad range of diseases including hemoglobinapathies and blood cancers. Diagnosing and treating these varied disorders brings us many types of technologies. In this WEEKLY, we’ll gather some of the best biotech has to offer the field of hematology.
THE HEMOGLOBIN PROTEiN
Hemoglobinapathies are the inherited disorders of hemoglobin, the all-important oxygen-transporting protein. Interestingly enough, there are only a few types of mutations that exist in the population because hemoglobin is such a crucial protein. Anyone born with a hemoglobin mutation most likely died shortly after birth due to the marked devastation of protein function.
The most common type of hemoglobinopathy is sickle cell anemia. This disorder is caused by a mutation in the hemoglobin gene causing the hemoglobin to clump together within the red blood cells, affecting the overall shape of the cell. Normal red blood cells are donut or disc shaped, while those affected are sickle or “C” shaped. These sickle-shaped cells have trouble passing through the blood vessels—especially as they narrow at the branch points to feed into tissues. Vaso-occlusive crises occur as the blood vessels become clogged with improperly shaped red blood cells, blocking the flow of oxygen into tissues. Severe pain and potential permanent damage to the affected tissue are symptoms of sickle cell anemia, stemming from the obstructed blood vessels.
As a single-gene disorder, it is a prime candidate for emerging gene therapy and genome editing technologies. Bluebird Bio’s (Cambridge, MA) LentiGlobin is a gene therapy treatment for sickle cell in Phase I and Sangamo Biosciences (Richmond, CA), in partnership with Biogen (Cambridge, MA), is currently developing a genome editing treatment.
DECIPHERING BLOOD CANCER
Like any other tissue in the body, the blood is susceptible to cancer. Blood cancers can affect any type of blood cell—white, red, or platelets—leading to their proliferation at the expense of the other blood cells. The three most common types of blood cancers are leukemia (cancers of the circulating white blood cells), lymphoma (cancer of white blood cells within lymphoid tissue such as lymph nodes or spleen), and myeloma (cancer of antibody-producing plasma cells)
Most blood cancers are the result of an acquired, rather than inherited, mutation in the bone marrow. The exact cause of most blood cancers is not known, but in some cases can be linked to radiation or chemical exposure. Certain viral infections have also been linked to blood cancers, including Epstein-Barr virus (the virus that causes mononucleosis), human T-cell leukemia virus, and human immunodeficiency virus. When these viruses infect white blood cells, they incorporate their own genetic material into the host cell chromosomes and occasionally disrupt genes involved in controlling cell growth and division.
DIAGNOSING DISEASES OF THE BLOOD
Sickle cell anemia is diagnosed using a genetic test that detects the single base change in the hemoglobin gene which causes the disease. Blood cancers, however, can be caused by a variety of different mutations, making it difficult to develop a “one test fits all” type of scenario.
Blood cancers are diagnosed by counting the number of each blood cell type, and determining if the amounts fall outside of the normal range. A diagnosis can be confirmed and further refined by looking at specific protein markers on the surface of blood cells. Blood cell counting and sorting is done via flow cytometry. By suspending cells in a stream of fluid, and then passing them through a “flow cell”—that allows only one cell at a time to flow past a detector—the number of each cell type can be determined using color coding. This process works by staining the blood cells with a fluorescent-labeled antibody before they are loaded into the flow cell. The fluorescent-labeled antibody recognizes and binds to specific marker proteins on the blood cell’s surface. The different marker proteins indicate what type of cell it is, or in some cases, if it is cancerous or not. As each cell passes by the detector, a laser beam is directed toward the cell, and records the presence or absence of a fluorescent label. Different markers may be detected simultaneously by using different colored fluorescent labels.
COCKTAIL FODDER: WHY IS SICKLE CELL ANEMIA MORE COMMON IN THE TROPICS?
Sickle cell anemia just so happens to be more common in tropical regions, such as sub-Saharan Africa and India. Enter the sickle cell trait—or, having just one copy of the gene for defective hemoglobin—which serves as a sort of protection measure against malaria.
Since half of the hemoglobin produced by those with sickle cell trait is normal, their red blood cells do not sickle for the most part. When infected by the malaria parasite, however, the oxygen concentration within the red blood cells drops—inducing hemoglobin clumping and the resultant red blood cell sickling. Sickled cells are recognized as damaged by the spleen, and therefore destroyed and removed from circulation—inadvertently also removing the malaria parasite. Having one copy of the gene for sickle cell disease presents no serious problems, yet gives a distinct survival advantage against the plethora of mosquitos in tropical populations.