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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Myelopoiesis
Ligation
Recovery
Peroxidase
Granulocyte Precursor Cells
Myeloid Cells
Cell culture
Cells
Immunoglobulin Fab Fragments
Flow cytometry
Antibodies
Cell growth
Protein-Tyrosine Kinases
Cell Aggregation
Bone
Blood
Agglomeration
Fetal Blood
Acute Myeloid Leukemia
Population

ASJC Scopus subject areas

  • Hematology

Cite this

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

CD38 ligation inhibits normal and leukemic myelopoiesis. / Elisabetta, Todisco; Suzuki, Toshio; Srivannaboon, Kleebsabai; Coustan-Smith, Elaine; Raimondi, Susana C.; Behm, Frederick G.; Kitanaka, Akira; Campana, Dario.

In: Blood, Vol. 95, No. 2, 15.01.2000, p. 535-542.

Research output: Contribution to journalArticle

Elisabetta, T, Suzuki, T, Srivannaboon, K, Coustan-Smith, E, Raimondi, SC, Behm, FG, Kitanaka, A & Campana, D 2000, 'CD38 ligation inhibits normal and leukemic myelopoiesis', Blood, vol. 95, no. 2, pp. 535-542.
Elisabetta T, Suzuki T, Srivannaboon K, Coustan-Smith E, Raimondi SC, Behm FG et al. CD38 ligation inhibits normal and leukemic myelopoiesis. Blood. 2000 Jan 15;95(2):535-542.
Elisabetta, Todisco ; Suzuki, Toshio ; Srivannaboon, Kleebsabai ; Coustan-Smith, Elaine ; Raimondi, Susana C. ; Behm, Frederick G. ; Kitanaka, Akira ; Campana, Dario. / CD38 ligation inhibits normal and leukemic myelopoiesis. In: Blood. 2000 ; Vol. 95, No. 2. pp. 535-542.
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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.",
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