Myelomastocytic overlap syndromes: biology, criteria, and relationship to mastocytosis

Although mast cells (MC) appear to be myeloid cells, MC lineage involvement in myelogenous malignancies has been described only rarely. Based on clona l evolution, biology of afflicted cells, and disease criteria, three major groups of patients have been recognized: The first meets criteria for both diagnoses 'systemic mastocytosis' and 'associated hematologic clonal non-ma st cell lineage disease (AHNMD)'. In such patients, myeloproliferative (MPS ) or myelodysplastic syndromes (MDS), or acute myeloid leukemia (AML) is di agnosed apart from mastocytosis. In a second group of patients, large numbe rs of very immature MC-lineage cells (metachromatically granulated blast-li ke cells) are detectable, but the criteria to diagnose mastocytosis are not met. These patients have advanced myeloid neoplasms (MDS or MPS with blast cell increase, or AML) and variably suffer from mediator-related symptoms (flush, GI-tract ulcer, diarrhoea, coagulopathy). In some cases, the diseas e mimics mast cell or basophilic leukemia. In contrast to basophilic leukem ia, however, the metachromatic cells are strongly KIT + and tryptase +. In contrast to true mast cell leukemia (MCL), MC do not form multifocal dense infiltrates in the bone marrow. Also, MC lack CD2 and CD25, and the C-KIT m utation Asp-816-Val. We propose the term 'myelomastocytic leukemia' or 'mye lodysplastic mast cell syndrome' for these cases. In a third group of patie nts, myeloid neoplasms (MDS, MPS, AML) show constitutive expression of MC-a ssociated antigens (tryptase, histamine) or mastocytosis-related gene defec ts (mutated C-KIT) without significant increase in metachromatic cells or c riteria of mastocytosis. Whether these neoplasms display aberrant gene expr ession (or gene defects) or represent 'pre-pre-mast cell leukemias', remain s unknown. (C) 2001 Elsevier Science Ltd. All rights reserved.