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 language | English |
|---|---|
| Pages (from-to) | 535-542 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 95 |
| Issue number | 2 |
| Publication status | Published - Jan 15 2000 |
Fingerprint
ASJC Scopus subject areas
- Hematology
Cite this
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 journal › Article
}
TY - JOUR
T1 - CD38 ligation inhibits normal and leukemic myelopoiesis
AU - Elisabetta, Todisco
AU - Suzuki, Toshio
AU - Srivannaboon, Kleebsabai
AU - Coustan-Smith, Elaine
AU - Raimondi, Susana C.
AU - Behm, Frederick G.
AU - Kitanaka, Akira
AU - Campana, Dario
PY - 2000/1/15
Y1 - 2000/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034650974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034650974&partnerID=8YFLogxK
M3 - Article
C2 - 10627459
AN - SCOPUS:0034650974
VL - 95
SP - 535
EP - 542
JO - Blood
JF - Blood
SN - 0006-4971
IS - 2
ER -