Myeloproliferative Neoplasm and Its Clinical Overview

Introduction:

Myeloproliferative neoplasms (MPNs) are clonal blood disorders characterized by an excess of differentiated blood (hematopoietic) cells. The three primary diseases that make up the myeloproliferative neoplasms are polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF).

If untreated, the myeloproliferative disorders lead to acute leukemia (blood and bone marrow cancer), which is life-threatening. Life expectancy for people with myeloproliferative neoplasms varies depending on the disease stage. The treatment depends on how severe the disease is. The mildness of the disorder affects a person's life expectancy with myeloproliferative neoplasms. It is also strengthened by effective treatment for the condition.

What Are the Types of Myeloproliferative Neoplasm?

Myeloproliferative neoplasms (MPNs) were divided into seven categories or types by the World Health Organization (WHO) in 2016:

• Chronic myeloid leukemia (CML) - Blood-cell cancer in bone marrow.

• Polycythemia vera (PV) - A blood disorder that causes an increase in blood cells.

• Chronic neutrophilic leukemia (CNL) - Excess of neutrophils.

• Primary myelofibrosis (PM) - Rare bone marrow disorder causing abnormalities in blood cell production.

• Unclassifiable (MPN-U).

• Essential thrombocythemia (EV) - A blood disorder that causes bone marrow to make excessive platelets.

• Chronic eosinophilic leukemia - Not otherwise specified and MPN.

What Are the Causes and Risk Factors of Myeloproliferative Neoplasm?

Host Genetic Diversity:

The sex and age of the host play a crucial part in the mutations of myeloproliferative neoplasms.

Single-nucleotide variations have been found in genome studies that raise the risk that such neoplasms will manifest.

Other single-nucleotide variants linked to mutations in the gene encodes:

• Calreticulin (CALR).

• The thrombopoietin receptor (MPL).

• Janus kinase 2 (JAK2).

One single-nucleotide variant haplotype was associated with myeloproliferative neoplasms, designated 46/1 (GGCC) and located in cis on the Janus kinase 2 (JAK2) allele.

The co-occurrence of stem-cell clones with calreticulin (CALR), the thrombopoietin receptor (MPL), and Janus kinase 2 (JAK2) mutations in the same person may be explained by these genetic predispositions.

Risk Factors: The increased risk of developing myeloproliferative neoplasm is mainly due to the age, sex, and family history of a person. Additionally, radiation exposure and certain toxins, such as benzene may also cause some types of myeloproliferative neoplasm.

What Are the Clinical Features of Myeloproliferative Neoplasm?

The symptoms of myeloproliferative neoplasm include:

1. Polycythemia Vera: Polycythemia vera is an abnormal and prevalent myeloproliferative neoplasm of all the blood-forming cells in the bone marrow (pan-myelopathy) resulting from the JAK2 gene, in rare instances, CALR or LNK mutations. The hallmarks of polycythemia vera are the following:

• Erythrocytosis (increased count of RBCs).

• Progressive rise in erythropoiesis (formation of red blood cells in the bone marrow).

• Granulopoiesis (formation of granulocytes in the bone marrow).

• Thrombopoiesis (formation of platelets in the bone marrow).

• Hyperviscosity of blood.

• Arterial and venous thrombosis (blood clots).

• Heart attacks.

• Ocular migraines (a severe form of headache involving the area around the eyes).

• Splenomegaly (enlargement of the spleen).

• Bone marrow failure.

• Myelofibrosis (type of bone marrow cancer).

• Acute leukemia.

2. Essential Thrombocythemia (EV): It is characterized by thrombocytosis due to the JAK2 gene and rarely by germline single-nucleotide variants, V617F, CALR, or MPL mutations. The complications include:

• Transient heart attacks.

• Ocular migraines.

• Acquired von Willebrand disease (a bleeding disorder).

• Pseudohyperkalemia (false-positive increase in potassium levels in the blood).

• Severe thrombocytosis.

• Acute leukemia.

• Myelofibrosis.

3. Primary Myelofibrosis:

It is the least frequent and most aggressive form of myeloproliferative neoplasm. It is characterized by:

• Extramedullary hematopoiesis-induced splenomegaly.

• Bone marrow fibrosis.

• Anemia (lack of enough healthy red blood cells).

• Organ failure and bone marrow failure.

• Pulmonary hypertension (a condition affecting blood vessels in the lungs).

• Acute leukemia.

How Is Myeloproliferative Neoplasm Diagnosed?

Trephine biopsy is one of the most important diagnostic procedures for myeloproliferative neoplasms. The other tests rely on red blood cells and bone marrow.

• Medical background information and physical exam.

• Blood test.

• Cytogenetic testing.

• Bone marrow aspiration and biopsy.

• Trephine biopsy.

What Is the Treatment for Myeloproliferative Neoplasm?

People with essential thrombocytosis have an average life expectancy. In contrast, people with polycythemia vera and primary myelofibrosis have median survival times of 14 and 27 years, respectively. Therefore, optimizing therapeutic benefits and preventing unneeded toxic effects is essential. Patients with myeloproliferative neoplasms should aim to reduce symptoms and avoid thrombosis and the development of myelofibrosis.

• Essential Thrombocytosis and Polycythemia Vera: Current therapeutic recommendations for polycythemia vera and essential thrombocytosis state that, in addition to the role of mutations, allele burdens, and the fact that thrombosis in polycythemia vera is provoked and related only to the hematocrit, patients 65 years of age or older and those with a history of thrombosis are at high risk for complications. Furthermore, polycythemia vera patients' difficulties do not differ by age, except for hepatic vein thrombosis in young women, but chemotherapy is still advised in both conditions.

• Chemotherapy and Phosphorus-32: Prevent thrombosis or extend survival. Both drugs are linked to an increased risk of leukemic transformation. Despite normalizing the platelet and leukocyte counts, hydroxyurea is less effective than Anagrelide or Aspirin in treating essential thrombocytosis patients. It only treats transient ischemic attacks and does not prevent arterial or venous thrombosis.

• Phlebotomy: It is a critical component of polycythemia vera treatment. The target hematocrit is under 45 percent for men and below 42 percent for women. Phlebotomy-related iron deficiency can help regulate red blood cell production, and it rarely requires treatment unless symptoms negatively affect the quality of life.

• Pegylated Interferon: It is preferable to hydroxyurea in patients under the age of 65 if a reduction in platelet count is required. Aspirin is adequate for microvascular episodes like ocular migraine and erythromelalgia caused by hyperactive platelets in polycythemia vera and essential thrombocytosis. However, Aspirin has no antithrombotic benefit.

• Myelofibrosis: Secondary myelofibrosis is the result of either polycythemia or essential thrombocytosis. Patients with CALR type 1 mutation may provide a survival benefit to patients with primary myelofibrosis.

• Targeted Therapies: Chemotherapy has been used. However, it does not prevent the extramedullary hematopoiesis linked to myelofibrosis and splenic irradiation. There are, however, two efficient, non-genotoxic therapies to deal with these issues: Ruxolitinib and Interferon.

• Ruxolitinib: An inhibitor of JAK1 and JAK2, alleviates symptoms and reduces splenomegaly.

• Pegylated Interferon: Effectively improves blood counts and effectively alleviates symptoms.

• Transplantation of Bone Marrow: A bone marrow transplant is the only effective myeloproliferative neoplasm therapy. However, the mortality associated with transplantation is high.

Conclusion:

Future therapies for myeloproliferative neoplasms face two challenges: accurate genetic identification of patients at risk for disease transformation and elimination of neoplastic blood (hematopoietic) stem cells to prevent leukemic transformation. Given these challenges, gene-expression profiling is likely the most helpful method for defining risk and identifying molecular pathways for targeted therapy because few oncogenes are recurrently mutated in these disorders. While new treatments for myeloproliferative neoplasms that target hematopoietic stem cells are being developed, efforts should be concentrated by the doctors on when and how to use these treatments that are currently known to be effective Ruxolitinib, Pegylated interferon, and bone marrow transplantation either separately or in combination, possibly with other therapies.