Systemic mastocytosis (SM) used to be classified as a type of myeloproliferative neoplasm (MPN), a group of rare blood cancers characterized by an overaccumulation of blood cells in the bone marrow.
SM is no longer considered a subclass of MPNs, but there remain several similarities between the two.
And while SM has been recategorized as a disease separate from MPNs, the overlap between them can delay the diagnosis process.
What is SM?
Systemic mastocytosis (SM) is a rare hematological disease characterized by mast cells that are overactive and accumulate in different parts of the body such as the bone marrow, liver, spleen, gastrointestinal tract and lymph nodes.
Symptoms
Because SM can lead to a wide range of symptoms, depending on which tissues are affected, it can be difficult to make a diagnosis.
Several symptoms that patients with SM experience are also common among individuals with MPNs. These may include the following:
- Gastrointestinal symptoms, including diarrhea, vomiting and abdominal pain.
- Itching and flushing of the skin.
- Fatigue.
- Headaches.
- Brain fog.
Some patients with SM might also have a non-mast-cell-mediated disease with similar symptoms, further complicating diagnosis. Additionally, patients may be diagnosed with SM and an associated MPN.
Read more about SM signs and symptoms
Disease genotype
A bone marrow biopsy can be used to differentiate between SM and MPNs. More than 90% of patients with SM also have a mutation in the c-KIT gene, which codes for a protein involved in the survival of mast cells.
What is the c-KIT gene?
Over 90% of patients with SM also have a mutation in the c-KIT gene, which codes for the protein CD117 transmembrane tyrosine kinase. CD117 is involved in the growth, survival and migration of mast cells. The most common c-KIT mutation among patients with SM is the D816V mutation, in which the amino acid aspartic acid is replaced with the amino acid valine in the protein.
On the other hand, around 70% of patients with MPNs have a mutation in the JAK2 gene. Mutations in the MPL and CALR genes have also been identified among individuals with MPNs.
Read more about SM testing and diagnosis
SM has been reclassified as a type of myeloid cancer rather than an MPN due in part to its distinct genotype.
Prognosis
The prognosis for both SM and MPNs varies widely, depending on several factors.
Patients with indolent SM tend to have a normal life expectancy, while individuals with SM and associated hematological neoplasm or mast cell leukemia have a shorter life expectancy. Prognosis may also be affected by other factors, including age, weight, low platelet count and low albumin levels.
Read more about SM prognosis
Similarly, there are significant variations in the prognosis of individuals with MPNs depending on which subtype of MPNs a patient has. For example, while patients with essential thrombocythemia often experience a normal life expectancy, triple-negative primary myelofibrosis (which is not associated with mutations in the JAK2, MPL or CALR genes) often results in a poorer prognosis.
