Chronic Myelogenous Leukemia(CML) also referred to as Chronic Myeloid Leukemia, or Acute Granulocytic Leukemia, is a rare type of cancer involving the blood cells and bone marrow. It is found in white blood cells which contain the oncogene, Philadelphia Chromosome (Ph+). Unlike other Leukemias, this particular blood cancer tends to progress more slowly than acute forms of leukemia, is found more often in older adults, usually males 45 years of age and older, and rarely occurs in children. It should be made clear that the Leukemias are not inherited diseases, and as with all other Leukemias, in most cases of CML, a caus, cannot be identified, however, it is thought that CML may evolve from environmental risk factors such as ionizing radiation, certain viral attacks, and other environmental carcinogens.
Chromosomes are the “set of instructions” for the body and control all the functions of cells. They are responsible for the production, division, and replication of daughter cells. These daughter cells should always have the correct replication of genetic programming (DNA), however, if there is something wrong with the chromosome then the “set of instructions” is also incorrect, and mutations can occur.
Unique to CML is the Philadelphia Chromosome (Ph+). Discovered in 1960 in Philadelphia by Dr. Peter Nowell, this translocation defect was found as a consistent finding in CML. Due to the limited techniques available at the time, Dr. Nowell and his colleagues didn’t have the capability to find what happened to the genetic material in the translocation of the chromosomes. It was not until 1972 that Janet Rowley, MD, discovered the first known chromosomal translocation. It was then discovered that the Philadelphia chromosome (Ph+), forms when chromosomes 9 and 22 break and exchange portions as seen in the figure below.
What occurs then is a new set of abnormal instructions for the cells involved, in this case, the white blood cells, which no longer function properly. This results in the generation of an abnormal BCR-ABL gene which becomes oncogenetic (cancer-causing). This oncogenetic BCR-ABL gene causes a deregulation of the protein, tyrosine kinase. Tyrosine kinase functions as the “on/off” switch for cellular activity, and in this particular disease, the cell does not have a functional “on” switch for apoptosis (programmed cell death) which allows for the propagation of new and healthy generations of the white cell line. What this means is that these abnormal cells continue to replicate unchecked and proliferate in the bone marrow and body. These cells do not grow and die like normal cells and they overcrowd healthy cells and damage the bone marrow along with other organs. In addition to involving the bone marrow, CML can cause secondary problems, such as an enlarged spleen (splenomegaly) and liver (hepatomegaly).
CML does not always reveal itself with overt signs and symptoms during its early phases. A patient may have CML for some time before diagnosis. Some signs and symptoms of CML are:
Loss of appetite
Pain or fullness below the ribs on the left side
CML can cause anemia and therefore fatigue because the unhealthy white blood cells are crowding out healthy red blood cells. At times, due to a shortage in healthy platelets (thrombocytopenia) which assist in controlling bleeding by helping to form clots, easy bleeding and bruising may occur. Conversely, an increased production of platelets (thrombocytosis) can cause excessive clot formation which may lead to cerebral vascular accidents (stroke) and myocardial infarction (heart attacks). Bone pain is not uncommon due to the neoplastic white blood cell build up in the bone marrow. The spleen becomes enlarged because the excess white blood cells are sequestered there. In some cases the spleen may become so enlarged it is at risk of rupturing. In addition, the white blood cells, although increased in number, and normally programmed to fight off infection, do not function properly, and the cells are unable to ward off infection.
There are three phases of CML. They are: (1) The Chronic Phase, the initial early phase; (2) The Accelerated Phase, the transitional phase when the disease begins to become aggressive; and (3)The Blastic Phase, a severe malignancy which becomes life threatening. Each phase is measured proportionally by the amount of diseased cells versus healthy cells in the patient’s blood and bone marrow. With a higher proportion of diseased cells present, the more advanced the stage will be.
Diagnostic work up for CML begins with a thorough history, and physical exam, checking for any lymphadenopathy (abnormalities in the lymph nodes), abdominal mass, or enlarged organs, evidence of ischemia, and of course, infection. Ancillary testing, including laboratory for a complete blood count, and blood chemistry are performed. Imaging, including chest x-ray and magnetic resonance imaging of suspicious sites are acquired. Finally, if CML is suspected, a bone marrow biopsy is performed. Confirmation ultimately utilizes laboratory testing for presence of oncogenetic markers including the Philadelphia chromosome and the BCR-ABL gene.
Treatment for CML is targeted to eradicate as many blood cells that contain the abnormal BCR-ABL gene as possible. Treatment cannot rid the patient of all the abnormal cells but it can help achieve remission of the disease. There are specific drugs targeting the deregulated protein produced by the BCR-ABL gene, tyrosine kinase. Such medications are:
Unfortunately, there is on occasion, no response to medication as the disease can become resistant to these interventions, in which case a blood stem cell transplant (bone marrow transplant) may offer a chance for patients. In bone marrow transplant therapies, high doses of chemotherapy are used to treat harvested blood forming cells in the bone marrow, with either autologous (self donated) or allogeneic (matching donor) stem cells. These are then re-infused into the patient. The hope is that new healthy cells will form and replace the diseased cells.
About The Author: Evamarie Hernandez, is a Senior Medical Laboratory Technology Student at Intellitec Medical Institute in Colorado Springs, Colorado, and an advanced Hematology student of Dr. Counce. Ms. Hernandez, an exceptional student, recently completed all didactic studies and is currently on externship. She will graduate with her Associates Degree in 2012.