A recent study published in Case Reports in Oncological Medicine describes a 63-year old man who was concurrently diagnosed with KIT-negative systemic mastocytosis (SM) and acute myeloid leukemia (AML).
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
In some individuals, SM may be diagnosed in combination with a blood cancer such as AML. This combination, called SM with an associated hematologic neoplasm (SM-AHN), is an advanced form of SM with a poor prognosis, as it is very challenging to treat.
“The case presented several atypical features, such as the lack of dermatologic manifestations, KIT negativity, the lack of elevated tryptase, and the presence of SM-AHN. These all present diagnostic and therapeutic challenges,” the report’s authors noted.
The patient originally presented to the hospital with an infection in his eye socket. There, he was found to have low levels of red blood cells, white blood cells and platelets. Further testing revealed abnormal levels of several white blood cells, indicative of AML.
Read more about SM prognosis
A bone marrow biopsy confirmed the diagnosis of AML, impacting 25% of the patient’s bone marrow cells. The biopsy also showed unusual clustering of mast cells, suggesting SM. Notably, though, KIT gene mutation testing came back negative.
The patient began chemotherapy with azacitidine and venetoclax, which he tolerated well. A repeat bone marrow biopsy showed a partial reduction in AML cells and an improvement in mastocytosis.
Eventually, the physicians deemed the patient to be in remission but with incomplete hematologic recovery. This means that the AML was fully treated, but his blood counts had not completely returned to normal levels.
After four more cycles of chemotherapy, during which the dose was repeatedly lowered due to low neutrophil levels, another bone marrow biopsy showed disease progression.
Ultimately, the patient’s physicians decided to switch to decitabine, another chemotherapy commonly used to treat AML. During this time, however, he developed pneumonia and ultimately passed away from sepsis.
This case highlights the complexities in diagnosing and treating SM-AHN, a rare, multifactorial disease. The lack of a KIT mutation raises further questions regarding the pathogenesis of his disease.
“Future research should be aimed at elucidating the molecular landscape of KIT-negative SM to uncover novel genetic or epigenetic drivers,” the authors concluded. “Collaborative efforts between clinical and research domains are essential to develop targeted therapies for this rare subgroup.”
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