Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature Can N. Kocabas, MD, Akif.

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Presentation transcript:

Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature Can N. Kocabas, MD, Akif S. Yavuz, MD, Peter E. Lipsky, MD, Dean D. Metcalfe, MD, Cem Akin, MD, PhD Journal of Allergy and Clinical Immunology Volume 115, Issue 6, Pages 1155-1161 (June 2005) DOI: 10.1016/j.jaci.2005.02.030 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Demonstration of the D816V c-kit mutation in the genomic DNA (A, patient 15) and mRNA (B, patient 1) in basophils and other hematopoietic lineages in mastocytosis. The codon 816 A/T c-kit mutation is indicated by the presence of a 99-bp band in the genomic DNA and a 157-bp band in the mRNA (cDNA) samples. HMC-1.1 and HMC-1.2 cells were included as negative and positive controls, respectively. C, Demonstration of the D816V c-kit mutation in an individual basophil with both wild-type and mutated alleles (right panel) in patient 15 (T to A change in antisense sequence). MW, Molecular weight. Journal of Allergy and Clinical Immunology 2005 115, 1155-1161DOI: (10.1016/j.jaci.2005.02.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Possibilities of lineage involvement patterns according to hypotheses of shared and nonshared committed progenitors between mast cells, basophils, and other lineages in systemic mastocytosis. Depending on whether the initial mutation occurs in an early (multipotential; B and D) or a late (committed; A and C) progenitor, the mutation is observed in different patterns in individual patients. The mutation would be detected only in mast cells and basophils if a dual committed progenitor is affected (A). Journal of Allergy and Clinical Immunology 2005 115, 1155-1161DOI: (10.1016/j.jaci.2005.02.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Flow-cytometric analysis of the Kit expression on the surface of basophils. Similar amounts of dim surface Kit expression were observed on basophils from patients with mastocytosis (n=12; A and B) and subjects without mastocytosis (C and D). The latter population included healthy volunteers (n=9) and patients with unexplained flushing or anaphylaxis but not mastocytosis (n=3). A and C, Isotype controls; B and D, cells stained with CD117-phycoerythrin (PE). Journal of Allergy and Clinical Immunology 2005 115, 1155-1161DOI: (10.1016/j.jaci.2005.02.030) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions