CD38 ligation inhibits normal and leukemic myelopoiesis

Todisco Elisabetta, Toshio Suzuki, Kleebsabai Srivannaboon, Elaine Coustan-Smith, Susana C. Raimondi, Frederick G. Behm, Akira Kitanaka, Dario Campana

Research output: Contribution to journalArticle

Abstract

CD38 is a transmembrane molecule whose expression varies during hematopoietic cell differentiation. We used stroma-supported cultures of human myeloid cells to assess the effects of CD38 ligation on myeloid differentiation. In 8 experiments with CD34+ cells purified from normal bone marrow or cord blood, flow cytometry used with antibodies to CD34 and myeloperoxidase (MPO) identified 4 cell populations after 7 days of culture. Addition of anti-CD38 (T16) to the cultures induced a profound reduction of the most mature (CD34-MPO++) cell population, which includes promyelocytes, myelocytes and metamyelocytes; mean (± SD) cell recovery was 12,8% ± 9.8% of that in parallel cultures with an isotype-matched control antibody. The suppressive effect of CD38 ligation on phenotypically more immature normal cells was inconsistent but generally less pronounced. Recovery of CD34++MPO- cells was 63.3% ± 24.4%, recovery of CD34[(+/-)] MPO- cells was 95.3% ± 35.1%, and recovery of CD34-MPO+ cells was 42.0% ± 18.7% of that in control cultures. However, anti-CD38 suppressed recovery of cells obtained from 6 patients with CD38+ acute myeloid leukemia; after 7-day cultures, cell recovery was 25.2% ± 21.7% of that in control cultures. Cell recovery was also reduced by F(ab')2 or Fab fragments of anti-CD38. CD38 ligation dramatically suppressed recovery of murine 32D myeloid cells transfected with human CD38 and cocultured with stroma (3.8% ± 7.3%; n = 7). CD38 ligation of CD38+ 32D cells also induced cell aggregation, tyrosine kinase activity, and Ca++ influx. We conclude that CD38 mediates signals that culminate in suppression of myeloid cell growth and survival.

Original languageEnglish
Pages (from-to)535-542
Number of pages8
JournalBlood
Volume95
Issue number2
Publication statusPublished - Jan 15 2000

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ASJC Scopus subject areas

  • Hematology

Cite this

Elisabetta, T., Suzuki, T., Srivannaboon, K., Coustan-Smith, E., Raimondi, S. C., Behm, F. G., Kitanaka, A., & Campana, D. (2000). CD38 ligation inhibits normal and leukemic myelopoiesis. Blood, 95(2), 535-542.