Abstract
The c-mpl ligand, thrombopoietin (TPO), is a physiologic regulator of platelet and megakaryocytic production, acting synergistically on thrombopoiesis with the growth factors interleukin 11 (IL-11), stem cell factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte- macrophage colony-stimulating factor. Because some of these growth factors, especially TPO and IL-11, are now being evaluated clinically to reduce chemotherapy-associated thrombocytopenia in cancer patients, we evaluated 25 acute myeloid leukemia (AML) samples to test whether TPO, IL-11, and other early-acting megakaryocyte growth factors can affect leukemic cell proliferation, cell cycle activation, and programmed cell death (PCD) protection. TPO induced proliferation in the majority of AML samples from an overall mean proportion of S-phase cells of 7.8% ± 1.5% to 14.5% ± 2.1% (p = 0.0006). Concurrent G0 cell depletion was found in 47.3% of AML samples. TPO-supported leukemic cell precursor (CFU-L) proliferation was reported in 5 of 17 (29.4%) of the samples with a mean colony number of 21.4 ± 9.6 x 105 cells plated. In 13 of 19 samples, a significant protection from PCD (from an overall mean value of 13% ± 0.7% to 8.8% ± 1.8%;p = 0.05) was detected after TPO exposure. Conversely, IL-11-induced cell cycle changes (recruitment from G0 to S phase) were detected in only 2 of 14 samples (14.2%). In addition, IL-11 showed little, if any, effect on CFU-L growth (mean colony number = 17.5 9.5) or apoptosis. Combination of TPO with IL-11 resulted in only a slight increase in the number of CFU-L, whereas IL-3 and stem cell factor significantly raised the mean colony numbers up to 119.2 ± 68.3 and 52.9 ± 22.1 x 105 cells plated, respectively. We conclude that TPO induces cell cycle activation in a significant proportion of cases and generally protects the majority of AML blast cells from PCD. On the other hand, IL-11 has little effect on the cell cycle or PCD. Combination of both TPO and IL- 11 is rarely synergistic in stimulating AML clonogenic growth. These findings may be useful for designing clinical studies aimed at reducing chemotherapy- associated thrombocytopenia in AML patients.
| Original language | English |
|---|---|
| Pages (from-to) | 1255-1263 |
| Number of pages | 9 |
| Journal | Experimental Hematology |
| Volume | 27 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 1999 |
Fingerprint
Keywords
- Acute myeloid leukemia
- Cell cycle
- Interleukin 11
- Programmed cell death
- Thrombopoietin
ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells. / Tafuri, Agostino; Lemoli, Roberto M.; Petrucci, Maria T.; Ricciardi, Maria R.; Fogli, Miriam; Bonsi, Laura; Ariola, Cristina; Strippoli, Pierluigi; Gregorj, Chiara; Petti, Maria C.; Tura, Sante; Mandelli, Franco; Bagnara, Gian P.
In: Experimental Hematology, Vol. 27, No. 8, 08.1999, p. 1255-1263.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells
AU - Tafuri, Agostino
AU - Lemoli, Roberto M.
AU - Petrucci, Maria T.
AU - Ricciardi, Maria R.
AU - Fogli, Miriam
AU - Bonsi, Laura
AU - Ariola, Cristina
AU - Strippoli, Pierluigi
AU - Gregorj, Chiara
AU - Petti, Maria C.
AU - Tura, Sante
AU - Mandelli, Franco
AU - Bagnara, Gian P.
PY - 1999/8
Y1 - 1999/8
N2 - The c-mpl ligand, thrombopoietin (TPO), is a physiologic regulator of platelet and megakaryocytic production, acting synergistically on thrombopoiesis with the growth factors interleukin 11 (IL-11), stem cell factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte- macrophage colony-stimulating factor. Because some of these growth factors, especially TPO and IL-11, are now being evaluated clinically to reduce chemotherapy-associated thrombocytopenia in cancer patients, we evaluated 25 acute myeloid leukemia (AML) samples to test whether TPO, IL-11, and other early-acting megakaryocyte growth factors can affect leukemic cell proliferation, cell cycle activation, and programmed cell death (PCD) protection. TPO induced proliferation in the majority of AML samples from an overall mean proportion of S-phase cells of 7.8% ± 1.5% to 14.5% ± 2.1% (p = 0.0006). Concurrent G0 cell depletion was found in 47.3% of AML samples. TPO-supported leukemic cell precursor (CFU-L) proliferation was reported in 5 of 17 (29.4%) of the samples with a mean colony number of 21.4 ± 9.6 x 105 cells plated. In 13 of 19 samples, a significant protection from PCD (from an overall mean value of 13% ± 0.7% to 8.8% ± 1.8%;p = 0.05) was detected after TPO exposure. Conversely, IL-11-induced cell cycle changes (recruitment from G0 to S phase) were detected in only 2 of 14 samples (14.2%). In addition, IL-11 showed little, if any, effect on CFU-L growth (mean colony number = 17.5 9.5) or apoptosis. Combination of TPO with IL-11 resulted in only a slight increase in the number of CFU-L, whereas IL-3 and stem cell factor significantly raised the mean colony numbers up to 119.2 ± 68.3 and 52.9 ± 22.1 x 105 cells plated, respectively. We conclude that TPO induces cell cycle activation in a significant proportion of cases and generally protects the majority of AML blast cells from PCD. On the other hand, IL-11 has little effect on the cell cycle or PCD. Combination of both TPO and IL- 11 is rarely synergistic in stimulating AML clonogenic growth. These findings may be useful for designing clinical studies aimed at reducing chemotherapy- associated thrombocytopenia in AML patients.
AB - The c-mpl ligand, thrombopoietin (TPO), is a physiologic regulator of platelet and megakaryocytic production, acting synergistically on thrombopoiesis with the growth factors interleukin 11 (IL-11), stem cell factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and granulocyte- macrophage colony-stimulating factor. Because some of these growth factors, especially TPO and IL-11, are now being evaluated clinically to reduce chemotherapy-associated thrombocytopenia in cancer patients, we evaluated 25 acute myeloid leukemia (AML) samples to test whether TPO, IL-11, and other early-acting megakaryocyte growth factors can affect leukemic cell proliferation, cell cycle activation, and programmed cell death (PCD) protection. TPO induced proliferation in the majority of AML samples from an overall mean proportion of S-phase cells of 7.8% ± 1.5% to 14.5% ± 2.1% (p = 0.0006). Concurrent G0 cell depletion was found in 47.3% of AML samples. TPO-supported leukemic cell precursor (CFU-L) proliferation was reported in 5 of 17 (29.4%) of the samples with a mean colony number of 21.4 ± 9.6 x 105 cells plated. In 13 of 19 samples, a significant protection from PCD (from an overall mean value of 13% ± 0.7% to 8.8% ± 1.8%;p = 0.05) was detected after TPO exposure. Conversely, IL-11-induced cell cycle changes (recruitment from G0 to S phase) were detected in only 2 of 14 samples (14.2%). In addition, IL-11 showed little, if any, effect on CFU-L growth (mean colony number = 17.5 9.5) or apoptosis. Combination of TPO with IL-11 resulted in only a slight increase in the number of CFU-L, whereas IL-3 and stem cell factor significantly raised the mean colony numbers up to 119.2 ± 68.3 and 52.9 ± 22.1 x 105 cells plated, respectively. We conclude that TPO induces cell cycle activation in a significant proportion of cases and generally protects the majority of AML blast cells from PCD. On the other hand, IL-11 has little effect on the cell cycle or PCD. Combination of both TPO and IL- 11 is rarely synergistic in stimulating AML clonogenic growth. These findings may be useful for designing clinical studies aimed at reducing chemotherapy- associated thrombocytopenia in AML patients.
KW - Acute myeloid leukemia
KW - Cell cycle
KW - Interleukin 11
KW - Programmed cell death
KW - Thrombopoietin
UR - http://www.scopus.com/inward/record.url?scp=0032765221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032765221&partnerID=8YFLogxK
U2 - 10.1016/S0301-472X(99)00063-6
DO - 10.1016/S0301-472X(99)00063-6
M3 - Article
C2 - 10428502
AN - SCOPUS:0032765221
VL - 27
SP - 1255
EP - 1263
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 8
ER -