Systemic mastocytosis is a rare disorder characterized by clonal proliferation, which results in abnormally high numbers of mast cells in the skin, bone marrow, and internal organs, such as liver, spleen, or lymph nodes. Mast cell leukemia and subvariants were stratified by the World Health Organization in 2016, as a subtype of systemic mastocytosis.

Here, we present a case of acute mast cell leukemia that was imatinib-sensitive, with well-known mutations in the oncogene, KIT (c.1565 T > G p.Phe522Cys), and in the splicing factor gene, SF3B1 (c.2098 A > G, p.Lys700Glu). Molecular cytogenetic studies showed that 26% of cells harbored the 46,XX,der(5)t(5;6)(q35;q24),t(10;16)(q26;q23) karyotype abnormality, confirmed with the fluorescence in-situ hybridization technique. Additionally, the patient showed severe hepatosplenomegaly with multiple retroperitoneal, mesenteric, and axillary adenopathies. Although the prognostic survival of patients with mast cell leukemia is around 6 months, this rare case, with a low-frequency (< 5%) p.Phe522Cys KIT mutation, was associated with complete remission and negative minimal residual disease, which lasted for 2.5 years; moreover, the mutation was not detectable after imatinib treatment. When the patient relapsed, the two mutations studied in KIT and SF3B1 genes reappeared, and a new clone emerged with the variant c.2465 A > C p.Asn822Thr, located in the activation loop of the KIT protein.

Molecular analyses of the KIT gene were essential for selecting the appropriate tyrosine-kinase inhibitor. Accurate drug selection can prevent possible resistance and facilitate adequate treatment of subsequent relapses.