ORIGIN OF HUMAN MAST-CELLS - DEVELOPMENT FROM TRANSPLANTED HEMATOPOIETIC STEM-CELLS AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Although mast cells are hematopoietic cells, little is known about the origin of their precursors in vivo. In this study, the origin (donor v recipient genotype) of human mast cells (MCs) was analyzed in a pati ent who underwent allogeneic bone marrow transplantation (BMT). The pa tient presented with secondary acute myeloid leukemia (French-American -British classification, M2) arising from refractory anemia with exces s of blast cells and bone marrow (BM) mastocytosis. Transplantation wa s performed in chemotherapy-induced complete remission. On days 88, 12 6, 198, and 494 after BMT, mast cells were enriched to homogeneity fro m bone marrow mononuclear cells (BM MNCs) by cell sorting for CD117(+) /CD34(-) cells. Purified mast cell populations were CD117(c-kit)(+) (> 95%), CD34(-) (<1%), CD3(-) (<1%), CD14(-) (<1%), and virtually free o f contaminating cells as assessed by Giemsa staining. The genotype of MCs was analyzed after amplification by polymerase chain reaction (PCR ) of a variable number tandem repeat (VNTR) region within intron 40 of the von Willebrand factor (VWF) gene. Unexpectedly, on days 88 and 12 6 after BMT, sorted MCs displayed recipient genotype as shown by vWF.V NTR-PCR. However, on days 198 and 494, PCR analysis showed a switch to donor genotype in isolated mast cells. peripheral brood (PB) and BM M NC as well as highly enriched (sorted) CD3(+) T cells (PB, BM), CB4(+) helper T cells (PB), CD8(+) T cells (PB), CD19(+) B cells (PB), CD14( +) monocytes (PB, BM), and CD34(+) precursor cells (BM) showed donor g enotype throughout the observation period. Together, these results pro vide evidence that human MCs developed in vivo from transplanted hemat opoietic stem cells. Engraftment and in vivo differentiation of MCs fr om early hematopoietic progenitor cells may be a prolonged process. (C ) 1994 by The American Society of Hematology.