A CASE OF MALIGNANT MASTOCYTOSIS WITH CIRCULATING MAST-CELL PRECURSORS - BIOLOGIC AND PHENOTYPIC CHARACTERIZATION OF THE MALIGNANT CLONE

The phenotypic and biologic properties of malignant cells in a case of aggressive mastocytosis with multi-organ involvement, circulating mas t cell precursors and absence of skin infiltrates were analyzed. Circu lating mast cell precursors were detected by immunostaining using anti bodies against mast cell tryptase as well as by electron microscopy. T hese progenitors were tryptase(+)/chymase(-) (MC(T)), and accounted fo r 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of th em contained metachromatic granules. As assessed by combined toluidine blue/immunofluorescence staining, the granulated mast cell precursors were found to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but no t basophil-related markers (CD11b (C3biR), CDw17 (lactosylceramide), C D123 (IL-3R alpha)) or monocyte-related antigens (CD14, CD15). Express ion of the mast cell growth factor (MGF) receptor, c-kit (CD117), was also demonstrable, whereas the skin mast cell marker C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit, recombi nant human (rh) stem cell factor (SCF = MGF), induced histamine releas e from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell-/basophil-agonist, was ineffective over the dose-range (10( -9) to 10(-7) M) tested. Analysis of mast cell antigens in malignant m astocytosis or mast cell leukemias may be helpful to establish a diagn osis and to determine the phenotype of the clone.