Myeloproliferative Neoplasms Disorders (MPN): It is the multiple disorders related to the bone marrow. In this group of disorders, the bone marrow forms too many RBCs, WBCs, and platelets, under an uncontrolled mechanism. Pluripotent hematopoietic stem cells self-renew, giving rise to a myeloid or lymphoid lineage that further differentiates into a variety of mature blood cells, such as red blood cells (RBCs), lymphocytes, granulocytes, megakaryocytes, and macrophages.
The hematopoietic process is determined by the bone marrow environment, growth factors, and transcription factors. Abnormal proliferation of one or more terminal bone marrow cell lines in peripheral blood results in a heterogeneous group of diseases termed Myeloproliferative neoplasms.
Myeloproliferative Neoplasms Disorders (MPN)
In 1951, William Dameshek coined the term myeloproliferative diseases, which has since been changed to myeloproliferative neoplasms (MPN) by the World Health Organization (WHO). It has further divided into six categories, chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MPF) are the four classic types of myeloproliferative neoplasms, chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia (CEL). Of the classic MPN types, CML is BCR-ABL1 positive, but PV, ET, and PMF are BCR-ABL1 negative.
Types and associated symptoms
Chronic myeloid leukemia (CML) – the overproduction of myeloblasts cells in blood and bone marrow marks this disorder. These myeloblasts further produce white blood cells that form myeloid cells. The situation gets critical with the increasing number of myeloblasts. This happens due to the presence of the BCR-ABL 1 gene in CML, resulting from the formation of the mutated chromosome, known as the Philadelphia chromosome. This mutated chromosome is formed by the interchange in the shorter arm of chromosome 9 and swapping places with the long arm of chromosome no 22. It is also known as chronic granulocytic leukemia or chronic myelogenous leukemia. Usually seen in older people and rarely in children.
Fore Reference:- https://www.cancer.org/cancer/types/chronic-myeloid-leukemia/about/what-is-cml.html
Symptoms – the particular symptoms of this cancer are fever, fatigue, abnormal bleeding, blood infection, anemia, pain in bone, swelling in the spleen unexplained bruises.
Polycythemia Vera (PV) – it is a cancer in which the no. of red blood cells elevates in the bone marrow. Along with this the no. of WBC and platelets also slightly increases. This thickens the blood, decreases the rate of blood flow, and gradually starts forming clots in the blood. It usually develops slowly, therefore, doesn’t produce any early symptoms. Although with some medications such as blood thickening agents, it can be managed well.
For Reference:- https://en.wikipedia.org/wiki/Polycythemia_vera
Symptoms – body acne, itching after taking a shower, numbness, loss of appetite, bloating, tingling and swelling in hands and feet, burning, weakness, headaches, joint pain (most often toe), shortness of breath, in severe cases if the clot reaches the heart, it can cause heart blockage.
Primary myelofibrosis (MPF) – In this disorder, the bone marrow’s functions are disrupted by excessive scar tissue formation and ultimately cause chronic inflammation. This makes it difficult for one marrow to form blood cells and instead RBS are formed in organs such as the spleen and liver. It can also happen as a progression of PCV.
For Reference:- http://www.mpnresearchfoundation.org/primary-myelofibrosis-pmf/
Symptoms – its symptoms mostly resemble to that of polycythemia vera. And includes the enlarged spleen, abdominal pain, early fullness feeling, and bloating, high pressure on liver vasculature, progressive anemia, and reduced production of RBCs, WBCs, and platelets. Fatigue, night sweats, itching, bone pain, inactivity, difficulty concentrating, fever, and weight loss.
Essential thrombocythemia (ET) – it’s the disorder of platelets, in which the bone marrow starts overproduction of clotting factor, platelets. The increasing no. of the same may lead to thrombus formation (a blood clot forms in the veins). In serious manifestation, it can lead to stroke, heart attack, and pulmonary embolism.
Symptoms – pain, redness, swelling in the legs and arms, chest pain, cough, shortness of breath, and nausea. Other common symptoms may include, slurred speech, dizziness, headache, numbness, weakness in the body, nosebleeds, bloody stools, and urine in blood.
Chronic neutrophilic leukemia (CNL) – this is the disorder caused due to the multiplication of only one kind of cell, i.e., neutrophils in this case due to mutation in one specific gene. This results in the overproduction of neutrophils, which accumulate in the peripheral blood system. These high numbers of neutrophils also cause the swelling in liver and spleen. It usually develops slowly but may also progress fast to acute leukemia.
Symptoms – bruises, fatigue, weight loss, enlarged liver and spleen, the feeling of fullness, night sweats, bone pain, sore throat, and fever.
Chronic eosinophilic leukemia (CEL) – This occurs due to the clonal proliferation of eosinophil precursors, leading to the overproduction of eosinophils in the peripheral blood system. This results in organ injury and organ failure and even death.
Symptoms – it has the same symptoms as CNL including, bruises, fatigue, weight loss, enlarged liver and spleen, the feeling of fullness, night sweats, bone pain, sore throat, and fever.
- Physical examination and medical history – physical examination includes the appearance of symptoms such as bruises, lumps, etc. And the medical history includes any prior disease or infection that the patient might have suffered, this includes any severe accident as well. Along with this any ongoing treatment, or past treatment.
- Complete Blood Count – it stands for a complete blood count. This is a very primary and essential diagnostic test in case of leukemia. It counts the number of RBCs, WBCs, Platelets, haemoglobin amount, etc.
- Blood chemical composition – it is done to check the presence of any secretary substances from organs. The high or low level can be an indication of abnormalities or infection.
- Biopsy and Bone Marrow aspiration – in this procedure, a hollow pipe is inserted into the hipbone to collect blood, bone, and bone marrow. Then the sample is examined under the microscope for any abnormalities in the cell morphology and activity observed by the pathologist.
- Cytogenetic analysis – this is the test to check the chromosome arrangement in the bone marrow sample. Any mutation such as broken, missing, rearranged, or extra chromosome. Any change can be a sign of cancer.
- Gene mutation test – this is the molecular test performed in the diagnostic laboratory, to check for the presence of BCR-ABL, Jak-2, etc.
For Reference:- https://www.leukaemia.org.au/blood-cancer/myeloproliferative-neoplasms/diagnosis/
- Phlebotomy – this is the diagnostic procedure in which the blood is drawn from the veins and examined under a microscope. Sometimes this is used as a treatment procedure to remove extra blood cells.
- Apheresis of platelets – it uses a special machine to collect blood from the patient body to remove platelets. The blood is then put through the blood cell separator and then the separated blood without platelets is inserted back into the patient. This is extensively used in the case of essential thrombocythemia especially.
- Transfusion therapy – it is the therapy given to the patient to remove the cancer-damaged cells with new red blood cells, white blood cells, and platelets.
- Chemotherapy – in this disorder systemic chemotherapy is used. In this, the chemo drugs are given orally or intravenously to remove the cancer cells.
- Radiation therapy – this therapy targets the spleen. High radiation such as X-rays is given externally. It also destroys the cancer cell form roots if targeted well.
- Medication – there are several drugs used to treat cancer. Such as Anagrelide is used to reduce blood clots in patients with high platelets. Prednisone and Danazol are used to treat a patient with primary myelofibrosis to cure anemia. Thalidomide, lenalidomide, and Pomalidomide are used to block the blood vessel to grow in tumor cells. Erythropoietic growth factors are used to increase blood cells from bone marrow.
- Splenectomy – it is the surgical removal of an enlarged spleen.
- Immunotherapy – this therapy is given to improve the immune reaction of patients. This is either done the boosting the natural immune response or by infusing the immune components synthesized in the lab to do so. Example of the latter method includes the use of interferon alpha and pegylated interferon alpha, which decrease the growth rate of tumor cells.
- Targeted therapy – this therapy uses substances that target the cancer cells to kill them. Such methods include the use of Tyrosine Kinase Inhibitors, used to block cancer growth signals. Another drug is Ruxolitinib, use to improve the condition of PCV.
- Stem cell transplantation – after chemotherapy, which destroys the normal blood-forming cells along with the cancer cells, stem cells are transplanted. The stem cells (immature) are taken from the patient or the donor and frozen till the completion of chemotherapy. After that, the stored stem cells are reinfused into the patient to restore normal blood cells.
For Reference:- https://www.ucsfhealth.org/conditions/myeloproliferative-disorders/treatment
Frequently Asked Questions
If the person is feeling any discomfort such as thick blood while bleeding, frequent nosebleeds, itching after taking a shower, body acne, unaccounted bruises or easy bruises, unusual lumps in the body, face flushing, weakness, heavy breathing and blood in urine, then they might be suffering from one of the Chronic Myeloproliferative Disorders. The person should seek medical help
No, these disorders are not passed on from one generation to another. Although the exact cause of the occurrence of such disorders is not known, researchers say that certain factors such as genetic mutation, unhealthy lifestyle, and obesity can be some reasons.
Some people get cancer, and some don’t, in spite of family history, because of faulty genes. There are some other factors required along with the presence of cancer genes. Such as the expression of a cancer gene, or no second mutation in the cancer gene, making it functionally okay. That gene might skip a generation and express in the next one. Other factors include the healthy lifestyle one maintains from the very beginning that, the cancer gene got suppressed or is completely curable.