Myeloproliferative Neoplasms: The Basics of Rare Blood Cancers

Myeloproliferative Neoplasms: The Basics of Rare Blood Cancers

Brief Summary of Disease
From birth, humans produce hundreds of millions of cells. This is what allows us to grow, to change, and to repair ourselves. Under certain circumstances, though, producing too many cells can prove to be a detriment. MPN, or myeloproliferative neoplasms, represents a group of rare blood cancers characterized by the excessive production of cells in the bone marrow, affecting fewer than six in 100,000 people.1,2 These excess cells, though sometimes harmless, can cause a variety of maladies resulting in anemia or enlargement of internal organs.2 MPN can affect anyone, but most patients are diagnosed in late adulthood.2,3 Prognosis varies widely among patients, as each form of the disease progresses differently; while some patients do not experience any symptoms, others may develop complications such as blood clots or leukemia.4

Etiology & Pathology
Specific forms of MPN may be caused by a genetic mutation allowing for the formation of an abnormally short chromosome called the Philadelphia Chromosome. This particular mutation is often associated with acute leukemia.5 Other forms of MPN are said to be Philadelphia-Chromosome-negative and include the following three diseases: polycythemia vera, essential thrombocythemia, and primary myelofibrosis.6 There are a variety of genetic mutations associated with Philadelphia-Chromosome-negative MPN, which can be inherited but more frequently are developed spontaneously.1,6 One common mutation is the V617F mutation in the JAK2 gene.6 This mutation is found in the genome of 96% of polycythemia vera patients, 55% of essential thrombocythemia patients, and 65% of primary myelofibrosis patients.6 The exact role of the mutation in disease onset is unknown, but it is believed to impact important cell signalling processes and allow for the over-production of cells.7 Though mutations like this increase an individuals likelihood of developing MPN, it is still not known what exactly causes the onset of symptoms.4 Following symptom onset, the disease often stays stable for a long time and progresses slowly.7 In some cases, particular forms of MPN may transform to become other forms or may transform into myeloid leukemia, a cancer of the bone marrow.7 Patients may also develop blood clots, which can occur both at early and late stages of the disease.4

Different forms of MPN are associated with different symptoms (Figure 1). When MPN is caused by an excess of red blood cells, the patient is said to have polycythemia vera MPN.4 This specific condition is associated with blurred or doubled vision, weight loss, and a buildup of pressure beneath the left rib.4 If the individual with MPN instead develops an excess of platelets, they are said to have essential thrombocythemia.4 Patients with this condition may experience sudden numbness or chest pains.4 Lastly, if the patient has an excess of undeveloped or abnormal stem cells, often called blasts, they are said to have primary myelofibrosis and may experience anemia and enlargement of organs like the spleen and liver.4 Some common symptoms associated with all forms of the disease are headache and fatigue.4

Diagnosis often begins with examining a blood sample to look for increased red blood cells, platelets, or white blood cells.8 Polycythemia vera is often identified by increased red blood cells and essential thrombocythemia is identified by increased platelet levels.8 In the case of primary myelofibrosis, patients often present with anemia and a blood count exam may reveal abnormal, teardrop shaped red blood cells and either an increased or decreased number of white blood cells.8 Next, a diagnosis can be confirmed through a bone marrow biopsy, where a sample of marrow is removed from the bone and examined under a microscope to count the number and type of cells present.8 A diagnosis can also be confirmed by genetic testing. This involves taking bone marrow samples and analyzing the individual chromosomes within the growing cells to look for mutations associated with MPN, like the JAK2 mutation.1

A patient’s prognosis is heavily dependent on the type and severity of MPN they have. Those with essential thrombocythemia often experience a normal life expectancy, while those with polycythemia vera or primary myelofibrosis may experience shortened lifespans.9 An individual with polycythemia vera has a typical lifespan of ten years after diagnosis, with diagnoses occurring at an average age of 61.3,9 Many individuals with MPN have slowly developing conditions and may never develop any associated complications.10

“Early and accurate diagnosis is important so that children can receive the supportive treatment they need and the disease can be monitored to identify changes in symptoms and the possible development of myeloid leukemia.”

Though MPN is usually observed in older adults, about 5% of diagnoses occur in childhood.7 Though the disease does have a genetic component, the exact genetic inheritance pattern is not well understood, and MPN is only considered familial in about 7% of all cases.1 Because of this, MPN screening is not a part of typical genetic prenatal testing and screening is usually only done when children begin to show symptoms. Diagnoses, much like in adults, can be done through a blood count or bone marrow exam.11 The course of treatment for children depends heavily on the severity of their symptoms and the type of MPN they present with. Some children may require chemotherapy or stem cell transplants, while others may only need occasional blood transfusions.12 Early and accurate diagnosis is important so that children can receive the supportive treatment they need and the disease can be monitored to identify changes in symptoms and the possible development of myeloid leukemia.

“...More research still needs to be done to further develop treatment options for individuals with MPN...”

Current Research
Research conducted within the last decade has revealed that genes such as JAK2 play an important role in driving the development of MPN diseases and increasing an individual’s likelihood of presenting symptoms. This has paved the way for the development of JAK2 inhibitors, drugs that a person with MPN can take to decrease the proliferation of cells in the bone marrow. A recent study out of Italy has compared clinical trial data for various JAK2 inhibitor drugs, finding that they are effective in reducing spleen volume in primary myelofibrosis patients, but identified an increased susceptibility to infections as a common side effect.13 Ruxolitinib, a pharmaceutical approved by the US Food and Drug Administration in 2011, represents one such drug.14 JAK2 inhibitors and other gene driver inhibitors continue to be a rich area of research being explored all over the world. Despite these great strides, more research still needs to be done to further develop treatment options for individuals with MPN and to better understand how and when the disease can transform to other forms of MPN or acute leukemia.

Relevant Resources
Canadian MPN Network
The Canadian MPN Network is a group that focuses on patient advocacy and public awareness of MPN. The Network is an annual conference that brings patients together with medical professionals.
Canadian MPN Group
The Canadian MPN Group advocates for improved research and treatment of MPN and provides up-to-date information about new research and clinical trial opportunities.

Works Cited:

1. Rumi E, Cazzola M. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017;129(6):680-692. doi:10.1182/blood-2016-10-695957

2. MPN Facts | Seattle Cancer Care Alliance.

3. Myeloproliferative Neoplasms | Cancer Network.

4. Symptoms, Diagnosis, & Risk Factors | Seattle Cancer Care Alliance.

5. NCI Dictionary of Cancer Terms. National Cancer Institute.

6. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(5):573-582. doi:10.1200/JCO.2010.29.8711

7. Childhood Myelodysplastic Syndromes and Myeloproliferative Neoplasms.

8. MPN diagnosis | Leukaemia Foundation.

9. Prognosis | Seattle Cancer Care Alliance.

10. About Mpns | Canadian MPN Network.

11. Childhood MDS and MPN diagnosis | Leukaemia Foundation.

12. Childhood MDS and MPN treatment | Leukaemia Foundation.

13. Passamonti F, Maffioli M. The role of JAK2 inhibitors in MPNs 7 years after approval. Blood. 2018;131(22):2426-2435. doi:10.1182/blood-2018-01-791491

14. Ajayi S, Becker H, Reinhardt H, et al. Ruxolitinib. Recent Results Cancer Res Fortschritte Krebsforsch Progres Dans Rech Sur Cancer. 2018;212:119-132. doi:10.1007/978-3-319-91439-8_6

Cite This Article:

Coles V., Chan G., Palczewski K., Lewis K., Ho J. Myeloproliferative Neoplasms: The Basics of Rare Blood Cancers. Illustrated by W. Y. Wu. Rare Disease Review. February 2019. DOI:10.13140/RG.2.2.13332.76164.

On Concluding Well...

On Concluding Well...

PhenomeCentral: A Tool for Improving Rare Disease Diagnosis

PhenomeCentral: A Tool for Improving Rare Disease Diagnosis