The receptor tyrosine kinase, EphB4 (HTK), promotes megakaryocytic and erythroid differentiation

Zhengyu Wang, Nobuyuki Miura, Andres Bonelli, Pamela Mole, David T. Scadden

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Abstract

EphB4 (HTK) is a member of Eph subfamily of receptor tyrosine kinases (RTKs). Eph B4 is expressed in primary CD34+ hematopoietic progenitors (J Biol Chem 269, 14211. 1994) as well as megakaryocytic cell lines, CMK and HEL. To assess whether EphB4 signaling regulates the differentiation of hematopoietic cells, we ectopically expressed human EphB4 in hematopoetic cells with the MSCV-GFP retroviral vector. EphB4 expression in the megakaryocytic leukemia cell line, CMK, promoted megakaryocytic differentiation with or without phorbol ester (PMA) simulation as demonstrated by increased cell surface CD41. However, over-expression of EphB4 in the promyelocytic cell line HL-60 had no effect on either granulocytic differentiation in the presence or absence of retinoic acid (ATRA) or monocytic differentiation in the presence or absence of PMA. Transduction of primary cord blood CD34+ cells with EphB4 resulted in lineage restricted marker expression including CD41 and glycophorin A, but not CD 14, CD33 or CD38 and enhanced BFU-E and CFU-Meg formation. Moreover, over-expression of EphB4 in CD34+CD38- cord blood cells resulted in accelerated depletion of that subpopulation of primitive cells. Our data suggest that Eph B4 may play a role in the early stages of hematopoiesis, enforcing preferential megakaryocytic and erythroid differentiation and possibly resulting in early progenitor cell depletion.

Original languageEnglish (US)
Pages (from-to)129b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Wang, Z., Miura, N., Bonelli, A., Mole, P., & Scadden, D. T. (2000). The receptor tyrosine kinase, EphB4 (HTK), promotes megakaryocytic and erythroid differentiation. Blood, 96(11 PART II), 129b.