Selectin-Dependent Organ Invasion and Prognostic Impact of Loss of CD2 in Systemic Mastocytosis

In non-advanced systemic mastocytosis (SM), mast cells (MC) express CD2 and CD58 and form focal tissue-aggregates, whereas in advanced SM, MC often lack CD2 and produce diffuse infiltration. To explore the role of CD2 in SM progression, CD2 + and CD2 − subclones of HMC-1.2 cells were generated and injected intraperitoneally into pfp/rag2 mice and scid mice. CD2 + HMC-1.2 cells formed focal MC lesions in the peritoneum and lungs of pfp/rag2 mice, while CD2 − HMC-1.2 cells produced more diffuse infiltration, resulting in reduced survival. To explore the mechanisms of organ invasion, E- and P-selectin-deficient scid mice (scid-select) were employed. While infiltrates of CD2 + and CD2 − HMC-1.2 cells were detected in scid mice, organ-infiltration was markedly reduced or absent in scid-select mice. Moreover, scid-select mice injected with CD2 + or CD2 − HMC-1.2 cells showed prolonged survival compared to control mice (p < 0.01). Correspondingly, CD2 was expressed more frequently on MC in patients with non-advanced SM compared to advanced SM, and patients with CD2 + SM were found to have prolonged survival compared to patients with CD2 − SM (p < 0.05). Together, E- and P-selectins mediate organ-invasion of neoplastic MC, whereas loss of CD2 contributes to a diffuse leukemic spread of MC and thus SM progression with reduced survival.