We are dealing with a group of pathologies that, just by their name, you know are going to be problematic.
Myeloproliferative neoplasms (MPN) are a diverse and varied set of hematologic neoplasms, chronic hematologic diseases, or blood cancers. Any of these three terms can be used to define them.
In MPNs, the cells that lose control are hematopoietic cells. Under normal conditions, these immature cells are the precursors of blood cells: red blood cells, white blood cells, and platelets.
Their progression to cancer is slow, and depending on the characteristics of the neoplasm, it will affect some blood cells or others. The types of myeloproliferative disorders include:
- Polycythemia vera, primary or erythremia, which leads to an increase in red blood cells, although there is also an increase in the other two cell types.
- In essential thrombocythemia, on the other hand, the excess production is of platelets.
- In chronic myeloid leukemia, the excessive production is of white blood cells. This is usually accompanied by a decrease in red blood cells and platelets (the constant and exaggerated production of white blood cells doesn’t allow for sharing too many resources).
- Within the MPNs, we also have myelofibrosis with myeloid metaplasia. This case is a bit different. There is an excess of fibrous tissue in the bone marrow, which causes the opposite effect of the previous cases: a decrease in all cell types. To compensate, the body produces blood cells in other organs such as the spleen or liver (the liver, whenever it can help, does so).
“Hey, but I’ve heard of another one called chronic granulocytic leukemia.”
Don’t worry, it’s actually the same as chronic myeloid leukemia. It’s an older term that has gradually fallen out of use, as “myeloid” is more accurate in referring to this pathology.
Genetic Classification: The Philadelphia Chromosome
There is a second classification sometimes used to refer to MPNs, based on the presence or absence of the Philadelphia chromosome. Fortunately, we are not referring to a person with 47 chromosomes, which would take the disease to the next level.
Philadelphia chromosome is the name given to an anomalous variant of chromosome 22. In this situation, a fragment of chromosome 9, which contains information from the ABL gene, fuses with chromosome 22 in the region where the BCR gene is located.
The result is a chromosome 22 (now called Philadelphia) with two fused genes in BCR::ABL, with part of this chromosome now found on 9, and vice versa.
Most people who develop chronic myeloid leukemia present with the Philadelphia chromosome, which is why it’s used to classify MPNs into those that have it—namely, leukemia—or those that don’t, which include all the others.
If anyone is curious, the fused gene produces an active BCR-ABL protein. In fact, this very activity, which promotes cell proliferation and suppresses apoptosis, is the main factor responsible for the pathology.
Different but Similar
As you might imagine, these neoplasms are grouped together because they share a number of common characteristics.
All of them arise from one or more mutations in a blood stem cell, or hematopoietic cell if you’re feeling pedantic. For the emergence and development of these mutations, the causes of myeloproliferation converge both genetic factors (the usual predisposition, with family history) and environmental factors (carcinogenic substances and lifestyles). Another thing they have in common is that these diseases are all complex.
However, they are not considered hereditary. Although there is a predisposition that can be inherited within the family, the mutations that ultimately lead to the disease arise during the patient’s lifetime and are not present from birth.
No one is born with this disease.
It is believed that Janus kinases (JAKs), a family of enzymes that catalyze the movement of phosphate groups, are among the main drivers of the pathological process when the Philadelphia chromosome is not present.
Another common detail is that the pathology tends to worsen over time. The first mutated cells not only produce an excess of blood cells, but they also divide into new altered copies.
We end up with more and more abnormal cells constantly producing an excessive amount of blood cells that accumulate in the bone marrow and circulatory system.
Since misfortunes seldom come alone, the process is sometimes accompanied by a strong release of cytokines over time. Many patients develop inflammatory conditions.
The basis for diagnosis is the same for all: blood and bone marrow analysis. But depending on the suspect (the increased cell group), different alterations are sought.
Similar but Different
The incidence, symptoms of myeloproliferative disorders, the treatment to follow… these pathologies are different enough to be distinguished in many aspects.
Polycythemia vera may take years to manifest. Symptoms include fatigue, headaches, itching after bathing, and noticeable redness. Sometimes, it is detected before symptoms appear through routine blood tests.
The increase in red blood cells causes the blood to thicken and a higher risk of blood clots, one of the major concerns.
At least the treatment is simple. Although there is no cure, blood removal to maintain normal red blood cell levels is sufficient most of the time. It can be combined with medications for severe symptoms.
Essential thrombocythemia shares symptoms with polycythemia vera, and they are due to the obstruction of blood vessels by clot formation. Coagulation is a process that deserves its own discussion.
The treatment is different from the previous one. Blood removal is only done in very severe situations, and the choice is medications to reduce platelet count and/or treat symptoms. When there is no bleeding among the symptoms, the use of aspirin is common.
With myeloid leukemia, bleeding is more frequent, accompanied by fatigue and night sweats, symptoms that worsen over time. They are due to the decrease in blood cell levels.
There is also an increased risk of infection because the number of normal white blood cells is lower than average.
Here, blood removal is of no use. Treatments include chemotherapy, aimed at blocking the abnormal protein responsible for the pathology (that BCR-ABL protein aberration born from a gene fusion), and even stem cell transplants if necessary.
Myelofibrosis presents the same symptoms as anemia: weakness, sweating, and general malaise. As the number of platelets and white blood cells also plummets without a parachute, we must add an increased risk of bleeding and infections.
Although medications can be used for treatment, severe cases require stem cell transplants.
Perhaps before having your blood drawn for analysis, you could have your saliva taken for genetic analysis by TellmeGen.
