Overview
Cytogenetics is the science of chromosome analysis. Most cells in the body have 46 chromosomes divided into 23 pairs. Each chromosome, in turn, contains thousands of units of DNA, all strung like beads on a double necklace and then coiled in the familiar double helix. Specific sections of DNA on the necklace are genes; they are the blueprint for everything in the body and how it is made and how it is controlled. Genes exert their influence by directing the production of a variety of enzymes and hormones, which are proteins that help to run the body. To study chromosomes, cells are obtained from blood or bone marrow samples and then put through some laboratory procedures that help make them easier to see. These samples are then studied under a microscope or in other ways. Certain recognizable changes - for example translocations of genetic material and differences in the number of chromosomes - can help doctors pinpoint some forms of leukemia and plan the best treatment. Laboratory procedures that might be performed in connection with genetic studies include fluorescence in situ hybridization, or FISH, a very sensitive test that can detect translocations, and polymerase chain reaction. The latter procedure, also known as PCR, allows scientists to search for a particular form of DNA and, if it is found, produce a large number of copies of it, thus making it much easier to detect in the laboratory. For example, it can be used to detect the presence of trace leukemia cells that are in such low concentrations that they could easily go unnoticed otherwise.
Translocations, Inversions, and Deletions
A translocation occurs when a section of DNA breaks off of one chromosome and attaches to another chromosome. Translocations can be visible under a microscope. In a laboratory report, a translocation may be noted in shorthand as t(9:22), which means that part of chromosome 9 has attached itself to chromosome 22. One common translocation is called the Philadelphia chromosome. It is found in people who have CML. Another type of chromosomal change is an inversion; it occurs when part of a chromosome breaks off, turns upside down, and reattaches to the original chromosome. It is written in reports as inv 16. A deletion, noted as del (5), means that part of a chromosome is missing, while an addition, noted as add (8), means that extra pieces of the chromosome are present. If a chromosome is missing entirely, such as chromosome 5, it is noted as -5. If there is an additional chromosome, such as chromosome 8, it is denoted as +8.
Chromosome Numbers
The normal number of chromosomes is 46. Sometimes, leukemic cells may have more or fewer than 46 chromosomes. When more than 50 chromosomes are present the condition is described as hyperdiploidy. If fewer than 45 chromosomes are present, the cells are said to be hypodiploid, and are known to be less sensitive to chemotherapy.
Immunophenotype
Immunophenotyping is the process of determining the types of proteins found on the surface of cells. It is done in a laboratory. It can be used to identify which antigens, or proteins, are expressed by normal and leukemic cells. Certain groups of antigens are found only on particular types of leukemia cells and so can help in distinguishing if and what form of the disease is present. The antigens are also called cluster-of-differentiation molecules; they are designated by number, such as CD3 and CD5. In the laboratory, monoclonal antibodies are used to identify which surface markers are present. A monoclonal antibody is a substance that is manufactured in a laboratory and is designed to react only with a particular protein on the surface of a cell. A monoclonal antibody is added to a sample of leukemia cells, and if the particular protein that it targets is present, a reaction is produced that can be detected in the laboratory. In most cases, immunophenotyping can clearly distinguish lymphocytic forms of leukemia from myelogenous forms of leukemia. It is also particularly helpful in diagnosing the particular subtypes of leukemia.
