Developmental, malignancy-related, and cross-species analysis of eosinophil, mast cell, and basophil Siglec-8 expression

Sherry A. Hudson, Harald Herrmann, Jian Du, Paul Cox, El-Bdaoui Haddad, Barbara Butler, Paul R. Crocker, Steven J. Ackerman, Peter Valent, Bruce S. Bochner

    Research output: Contribution to journalArticlepeer-review

    55 Citations (Scopus)

    Abstract

    The aim of this study is to determine when during hematopoiesis Siglec-8 gets expressed, whether it is expressed on hematologic malignancies, and if there are other non-human species that express Siglec-8.

    Siglec-8 mRNA and cell surface expression was monitored during in vitro maturation of human eosinophils and mast cells. Flow cytometry was performed on human blood and bone marrow samples, and on blood samples from dogs, baboons, and rhesus and cynomolgus monkeys.

    Siglec-8 is a late maturation marker. It is detectable on eosinophils and basophils from subjects with chronic eosinophilic leukemia, chronic myelogenous leukemia, and on malignant and non-malignant bone marrow mast cells, as well as the HMC-1.2 cell line. None of the Siglec-8 monoclonal antibodies tested recognized leukocytes from dogs, baboons, and rhesus and cynomolgus monkeys.

    Siglec-8-based therapies should not target immature human leukocytes but should recognize mature and malignant eosinophils, mast cells, and basophils. So far, there is no suitable species for preclinical testing of Siglec-8 monoclonal antibodies.

    Original languageEnglish
    Pages (from-to)1045-1053
    Number of pages9
    JournalJournal of Clinical Immunology
    Volume31
    Issue number6
    DOIs
    Publication statusPublished - Dec 2011

    Keywords

    • Siglec-8
    • Eosinophils
    • Mast cells
    • Basophils
    • Expression
    • Hematologic malignancies
    • Cell lines
    • Mouse siglec
    • In vitro
    • Lewis-X
    • Blood
    • Apoptosis
    • Inhibition
    • Engagement
    • Receptors
    • Induction
    • Mechanism

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