Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells

Agostino Tafuri, Roberto M. Lemoli, Maria T. Petrucci, Maria R. Ricciardi, Miriam Fogli, Laura Bonsi, Cristina Ariola, Pierluigi Strippoli, Chiara Gregorj, Maria C. Petti, Sante Tura, Franco Mandelli, Gian P. Bagnara

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1255-1263
Number of pages9
JournalExperimental Hematology
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 1999

Fingerprint

Interleukin-11
Thrombopoietin
Myeloid Cells
Acute Myeloid Leukemia
Cell Cycle
Cell Death
Intercellular Signaling Peptides and Proteins
Stem Cell Factor
Interleukin-3
S Phase
Thrombocytopenia
Thrombopoiesis
Drug Therapy
Megakaryocytes
Cytoprotection
Granulocyte-Macrophage Colony-Stimulating Factor
Growth
Interleukin-6
Blood Platelets
Cell Proliferation

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 journalArticle

Tafuri, A, Lemoli, RM, Petrucci, MT, Ricciardi, MR, Fogli, M, Bonsi, L, Ariola, C, Strippoli, P, Gregorj, C, Petti, MC, Tura, S, Mandelli, F & Bagnara, GP 1999, 'Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells', Experimental Hematology, vol. 27, no. 8, pp. 1255-1263. https://doi.org/10.1016/S0301-472X(99)00063-6
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. / Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells. In: Experimental Hematology. 1999 ; Vol. 27, No. 8. pp. 1255-1263.
@article{b17a4f3ccf084fa4a5c8bd1b6884322a,
title = "Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells",
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.",
keywords = "Acute myeloid leukemia, Cell cycle, Interleukin 11, Programmed cell death, Thrombopoietin",
author = "Agostino Tafuri and Lemoli, {Roberto M.} and Petrucci, {Maria T.} and Ricciardi, {Maria R.} and Miriam Fogli and Laura Bonsi and Cristina Ariola and Pierluigi Strippoli and Chiara Gregorj and Petti, {Maria C.} and Sante Tura and Franco Mandelli and Bagnara, {Gian P.}",
year = "1999",
month = "8",
doi = "10.1016/S0301-472X(99)00063-6",
language = "English",
volume = "27",
pages = "1255--1263",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "8",

}

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 -