Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome

Britta Will, Masahiro Kawahara, Julia P. Luciano, Ingmar Bruns, Samir Parekh, Connie L. Erickson-Miller, Manuel A. Aivado, Amit K. Verma, Ulrich G. Steidl

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 μg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2- deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xeno-transplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients withAML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.

Original languageEnglish (US)
Pages (from-to)3899-3908
Number of pages10
JournalBlood
Volume114
Issue number18
DOIs
StatePublished - Oct 29 2009

Fingerprint

Thrombopoietin Receptors
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Bone Marrow Cells
Bone
Cells
Thrombocytopenia
Apoptosis
Hematopoiesis
Bromodeoxyuridine
eltrombopag
Cell Count
Transplantation
Molecules
Testing

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. / Will, Britta; Kawahara, Masahiro; Luciano, Julia P.; Bruns, Ingmar; Parekh, Samir; Erickson-Miller, Connie L.; Aivado, Manuel A.; Verma, Amit K.; Steidl, Ulrich G.

In: Blood, Vol. 114, No. 18, 29.10.2009, p. 3899-3908.

Research output: Contribution to journalArticle

Will, Britta ; Kawahara, Masahiro ; Luciano, Julia P. ; Bruns, Ingmar ; Parekh, Samir ; Erickson-Miller, Connie L. ; Aivado, Manuel A. ; Verma, Amit K. ; Steidl, Ulrich G. / Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. In: Blood. 2009 ; Vol. 114, No. 18. pp. 3899-3908.
@article{5f92e5b222374f2dbeced5f7d0b3d823,
title = "Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome",
abstract = "Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 μg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56{\%}; SD, 28{\%}). Eltrombopag neither led to increased 5-bromo-2- deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xeno-transplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients withAML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.",
author = "Britta Will and Masahiro Kawahara and Luciano, {Julia P.} and Ingmar Bruns and Samir Parekh and Erickson-Miller, {Connie L.} and Aivado, {Manuel A.} and Verma, {Amit K.} and Steidl, {Ulrich G.}",
year = "2009",
month = "10",
day = "29",
doi = "10.1182/blood-2009-04-219493",
language = "English (US)",
volume = "114",
pages = "3899--3908",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "18",

}

TY - JOUR

T1 - Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome

AU - Will, Britta

AU - Kawahara, Masahiro

AU - Luciano, Julia P.

AU - Bruns, Ingmar

AU - Parekh, Samir

AU - Erickson-Miller, Connie L.

AU - Aivado, Manuel A.

AU - Verma, Amit K.

AU - Steidl, Ulrich G.

PY - 2009/10/29

Y1 - 2009/10/29

N2 - Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 μg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2- deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xeno-transplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients withAML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.

AB - Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, we studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. Malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 μg/mL. On the contrary, we observed a moderate, statistically nonsignificant (P = .18), decrease of numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag neither led to increased 5-bromo-2- deoxyuridine incorporation, decreased apoptosis, an increase of malignant self-renewal, nor enhanced in vivo engraftment in xeno-transplantations. Furthermore, we found that Eltrombopag was capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients withAML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for treatment of thrombocytopenia in AML and MDS.

UR - http://www.scopus.com/inward/record.url?scp=70449726874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449726874&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-04-219493

DO - 10.1182/blood-2009-04-219493

M3 - Article

VL - 114

SP - 3899

EP - 3908

JO - Blood

JF - Blood

SN - 0006-4971

IS - 18

ER -