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Origin of human mast cells: development from transplanted hematopoietic
stem cells after allogeneic bone marrow transplantation
M Fodinger, G Fritsch, K Winkler, W Emminger, G Mitterbauer, H Gadner, P Valent and C Mannhalter
Department of Molecular Biology, University of Vienna, Austria.
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 patient who
underwent allogeneic bone marrow transplantation (BMT). The patient
presented with secondary acute myeloid leukemia (French-American- British
classification, M2) arising from refractory anemia with excess of blast
cells and bone marrow (BM) mastocytosis. Transplantation was performed in
chemotherapy-induced complete remission. On days 88, 126, 198, and 494
after BMT, mast cells were enriched to homogeneity from 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 of 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 126 after BMT, sorted MCs
displayed recipient genotype as shown by vWF.VNTR-PCR. However, on days 198
and 494, PCR analysis showed a switch to donor genotype in isolated mast
cells. Peripheral blood (PB) and BM MNC as well as highly enriched (sorted)
CD3+ T cells (PB, BM), CD4+ helper T cells (PB), CD8+ T cells (PB), CD19+ B
cells (PB), CD14+ monocytes (PB, BM), and CD34+ precursor cells (BM) showed
donor genotype throughout the observation period. Together, these results
provide evidence that human MCs developed in vivo from transplanted
hematopoietic stem cells. Engraftment and in vivo differentiation of MCs
from early hematopoietic progenitor cells may be a prolonged process.
Volume 84,
Issue 9,
pp. 2954-2959,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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