Abstract
KIT D816 mutations (KIT D816mut) are strongly associated with systemic mastocytosis (SM) but are also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor in combination with core binding factor (CBF) fusion genes. Here, we evaluated the clinical and molecular features of KIT D816mut/CBF-negative (CBFneg) AML, a previously uncharacterized combination. All KIT D816mut/CBFneg cases (n = 40) had histologically proven SM with associated AML (SM-AML). Molecular analyses revealed at least one additional somatic mutation (median, n = 3) beside KIT D816 (e.g., SRSF2, 38%; ASXL1, 31%; RUNX1, 34%) in 32/32 (100%) patients. Secondary AML evolved in 29/40 (73%) patients from SM ± associated myeloid neoplasm. Longitudinal molecular and cytogenetic analyses revealed the acquisition of new mutations and/or karyotype evolution in 15/16 (94%) patients at the time of SM-AML. Median overall survival (OS) was 5.4 months. A screen of two independent AML databases (AMLdatabases) revealed remarkable similarities between KIT D816mut/CBFneg SM-AML and KIT D816mut/CBFneg AMLdatabases (n = 69) with regard to KIT D816mut variant allele frequency, mutation profile, aberrant karyotype, and OS suggesting underlying SM in a significant proportion of AMLdatabases patients. Bone marrow histology and reclassification as SM-AML has important clinical implications regarding prognosis and potential inclusion of KIT inhibitors in treatment concepts.
Highlights
According to the World Health Organization (WHO) classification, advanced systemic mastocytosis comprises aggressive SM, SM with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia [1,2,3]
We report here on a large series of 40 patients with morphologically proven KIT D816mut/CBFneg SM-acute myeloid leukemia (AML)
Similar to previous reports concerning the molecular profile of advSM, all patients with SM with associated AML (SM-AML) had at least one additional somatic mutation, most frequently affecting TET2, SRSF2, ASXL1, RUNX1, and NPM1
Summary
According to the World Health Organization (WHO) classification, advanced systemic mastocytosis (advSM) comprises aggressive SM, SM with an associated hematologic neoplasm (SM-AHN), and mast cell leukemia [1,2,3]. SMAHN is the most frequent subtype diagnosed in up to 80% of advSM patients [4]. The AHN is characterized in >90% of patients as a myeloid neoplasm, e.g., myelodysplastic/ myeloproliferative neoplasm unclassifiable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
