Abstract
In this study we report our data on effects of early-acting megakaryocyte growth factors, particularly the c-mpl ligand also known as thrombopoietin (TPO) and interleukin-11 (IL-11), on cell proliferation and apoptosis (Apo) of primary acute myeloid leukemia (AML) cells. A proliferative response to TPO was noticed in the majority of AML samples (17/19) with an average increase of S-phase cells from 7.8% ± 1.5 to 14.5% ± 2.1 (p=0.0006). Resulting cell cycle activation did not always correlate with expression of the c-mpl receptor, although it was coupled, in the majority of samples, by an average decrease of apoptotic cells from 13% ±0.7 to 8.8% ±1.8 (p=0.05). Clonogenic cell growth (CFU-L) was confirmed in 5/17 of the samples with a mean colony number of 21.4 ±9.6 × 105 cells plated. Conversely, effects of IL-11 on AML cells demonstrated that cell cycle changes (recruitment from G0 to S phase) were promoted only in a minority of samples (2/14) and there was little, if any, effect on CFU-L growth (mean colony number=17.5±9.5) or Apo (from 13% ±0.7 to 13.3±1.9). Combination of TPO with IL-11 induced a slight increase of clonogenic cell growth, while the addition of IL-3 or SCF to the c-mpl ligand significantly raised the mean colony numbers up to 119.2±68.3 and 52.9±22.1 × 105 cells plated, respectively. In summary, TPO shows activity on AML cells by stimulating their proliferation in a significant proportion of cases and generally protecting the majority of AML blast cells from induction of Apo. Conversely, IL-11 exerts little effect on the cell cycle activation and Apo. These data help to understand regulation of myeloid leukemia cell growth and should be considered in the clinical use of early-acting megakaryocyte growth factors in acute leukemia.
| Original language | English |
|---|---|
| Pages (from-to) | 179-190 |
| Number of pages | 12 |
| Journal | Leukemia and Lymphoma |
| Volume | 40 |
| Issue number | 1-2 |
| Publication status | Published - 2001 |
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Keywords
- Apoptosis
- Cell cycle
- Early-acting megakaryocyte growth factors
- Interleukin-11
- Thrombopoietin
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
Thrombopoietin, interleukin -11, and early-acting megakaryocyte growth factors in human myeoloid leukemia cells. / Petrucci, M. T.; Ricciardi, M. R.; Gregorj, C.; Ariola, C.; Mazzola, F.; Fogli, M.; Lemoli, R. M.; Tafuri, A.
In: Leukemia and Lymphoma, Vol. 40, No. 1-2, 2001, p. 179-190.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thrombopoietin, interleukin -11, and early-acting megakaryocyte growth factors in human myeoloid leukemia cells
AU - Petrucci, M. T.
AU - Ricciardi, M. R.
AU - Gregorj, C.
AU - Ariola, C.
AU - Mazzola, F.
AU - Fogli, M.
AU - Lemoli, R. M.
AU - Tafuri, A.
PY - 2001
Y1 - 2001
N2 - In this study we report our data on effects of early-acting megakaryocyte growth factors, particularly the c-mpl ligand also known as thrombopoietin (TPO) and interleukin-11 (IL-11), on cell proliferation and apoptosis (Apo) of primary acute myeloid leukemia (AML) cells. A proliferative response to TPO was noticed in the majority of AML samples (17/19) with an average increase of S-phase cells from 7.8% ± 1.5 to 14.5% ± 2.1 (p=0.0006). Resulting cell cycle activation did not always correlate with expression of the c-mpl receptor, although it was coupled, in the majority of samples, by an average decrease of apoptotic cells from 13% ±0.7 to 8.8% ±1.8 (p=0.05). Clonogenic cell growth (CFU-L) was confirmed in 5/17 of the samples with a mean colony number of 21.4 ±9.6 × 105 cells plated. Conversely, effects of IL-11 on AML cells demonstrated that cell cycle changes (recruitment from G0 to S phase) were promoted only in a minority of samples (2/14) and there was little, if any, effect on CFU-L growth (mean colony number=17.5±9.5) or Apo (from 13% ±0.7 to 13.3±1.9). Combination of TPO with IL-11 induced a slight increase of clonogenic cell growth, while the addition of IL-3 or SCF to the c-mpl ligand significantly raised the mean colony numbers up to 119.2±68.3 and 52.9±22.1 × 105 cells plated, respectively. In summary, TPO shows activity on AML cells by stimulating their proliferation in a significant proportion of cases and generally protecting the majority of AML blast cells from induction of Apo. Conversely, IL-11 exerts little effect on the cell cycle activation and Apo. These data help to understand regulation of myeloid leukemia cell growth and should be considered in the clinical use of early-acting megakaryocyte growth factors in acute leukemia.
AB - In this study we report our data on effects of early-acting megakaryocyte growth factors, particularly the c-mpl ligand also known as thrombopoietin (TPO) and interleukin-11 (IL-11), on cell proliferation and apoptosis (Apo) of primary acute myeloid leukemia (AML) cells. A proliferative response to TPO was noticed in the majority of AML samples (17/19) with an average increase of S-phase cells from 7.8% ± 1.5 to 14.5% ± 2.1 (p=0.0006). Resulting cell cycle activation did not always correlate with expression of the c-mpl receptor, although it was coupled, in the majority of samples, by an average decrease of apoptotic cells from 13% ±0.7 to 8.8% ±1.8 (p=0.05). Clonogenic cell growth (CFU-L) was confirmed in 5/17 of the samples with a mean colony number of 21.4 ±9.6 × 105 cells plated. Conversely, effects of IL-11 on AML cells demonstrated that cell cycle changes (recruitment from G0 to S phase) were promoted only in a minority of samples (2/14) and there was little, if any, effect on CFU-L growth (mean colony number=17.5±9.5) or Apo (from 13% ±0.7 to 13.3±1.9). Combination of TPO with IL-11 induced a slight increase of clonogenic cell growth, while the addition of IL-3 or SCF to the c-mpl ligand significantly raised the mean colony numbers up to 119.2±68.3 and 52.9±22.1 × 105 cells plated, respectively. In summary, TPO shows activity on AML cells by stimulating their proliferation in a significant proportion of cases and generally protecting the majority of AML blast cells from induction of Apo. Conversely, IL-11 exerts little effect on the cell cycle activation and Apo. These data help to understand regulation of myeloid leukemia cell growth and should be considered in the clinical use of early-acting megakaryocyte growth factors in acute leukemia.
KW - Apoptosis
KW - Cell cycle
KW - Early-acting megakaryocyte growth factors
KW - Interleukin-11
KW - Thrombopoietin
UR - http://www.scopus.com/inward/record.url?scp=0035145597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035145597&partnerID=8YFLogxK
M3 - Article
VL - 40
SP - 179
EP - 190
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 1-2
ER -