An immature immunophenotype of bone marrow mast cells predicts for multilineage D816V KIT mutation in systemic mastocytosis

Abstract

D816V KIT mutation of bone marrow (BM) mast cells (MC) is a common feature to systemic mastocytosis (SM) patients. Nevertheless, occurrence of the KIT mutation in BM cell compartments other than MC is associated with progression to more aggressive forms of the disease and poor outcome in indolent SM (ISM). Here, we assessed the potential association between the immunophenotype of MC and multilineage KIT mutation in the BM of SM patients through the investigation of the flow cytometric protein expression profile (PEP) of bone marrow mast cells (BMMC) from 70 control individuals and 206 SM patients, classified according to the WHO (World Health Organization), and the degree of involvement of BM hematopoiesis by the D816V KIT mutation; additionally, we developed a score-based class prediction algorithm for the detection of SM cases with multilineage mutation. Our results show that aberrant expression of CD25 with a FceRI lo , FSC lo , SSC lo and CD45 lo immature phenotype of BMMC, in the absence of coexisting normal MC in the BM, was associated with multilineage involvement by the D816V KIT mutation, regardless of the diagnostic subtype of the disease (for example, indolent vs aggressive SM), which supports the utility of the immunophenotype of BMMC as a surrogate marker to screen for multilineage KIT mutation in ISM.Leukemia (2012) 26, 951 --958;

Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications

“…Overall, 64 of 192 patients included in this study have been included in previously reported series of systemic mastocytosis patients by the REMA. [19][20][21][22] …”

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

“…Further, comprehensive immunophenotyping has shown that an immature BM MC phenotype (CD25 1 /FceRI lo /FSC lo / SSC lo /CD45 lo ), in the absence of coexisting normal MC in the BM, correlated with multilineage hematopoietic involvement by KITD816V, regardless of the WHO SM subtype [74]. In contrast, BM MC from patients with ISM subtypes displayed a mature activated MC phenotype (e.g., increased expression of MC activation markers CD63, CD69, and CD203c in patients with BMM) [75].…”

Mast cell leukemia

“…8,27 It follows that MC from MCL may express immaturity markers such as CD123, CD34, HLA-DR, and display reduced expression of CD117 and FceRI. The immature phenotype is correlated with multilineage KIT mutations in bone marrow and a poor prognosis.…”

“…8 Nevertheless, the prognostic significance of these observations for predicting clinical outcome in patients with SM requires further investigation. Therapeutic options are limited and the disease is most often fatal within a few months.…”