Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone

Roni Tamari, Carolina Schinke, Tushar Bhagat, Michael Roth, Ira Braunschweig, Britta Will, Ulrich G. Steidl, Amit K. Verma

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Lenalidomide (Len) is clinically indicated in myelodysplastic syndrome (MDS) but its use is limited by significant thrombocytopenia. Eltrombopag (EP) is a thrombopoietin receptor agonist that can stimulate platelet production and has shown preclinical efficacy in inhibiting leukemic cell proliferation. Thus, we determined the preclinical efficacy and safety of combining Len and EP in acute myelogenous leukemia (AML) and MDS. We found that single agent treatment of leukemia and lymphoma cell lines with EP and Len showed differential sensitivities to either agent. Combination therapy did not result in reversal of anti-malignant effects on these cells. Furthermore, the combination of Len and EP resulted in significant inhibitory effects on growth of leukemic colonies in the majority of primary MDS and AML samples. Most importantly, EP was able to reverse the anti-megakaryopoietic effects of Len in primary MDS patient samples. These results provide a preclinical rationale for the use of this combination in MDS and AML.

Original languageEnglish (US)
Pages (from-to)2901-2906
Number of pages6
JournalLeukemia and Lymphoma
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Myelodysplastic Syndromes
Acute Myeloid Leukemia
Clone Cells
Thrombopoietin Receptors
Thrombocytopenia
Lymphoma
Leukemia
Blood Platelets
Cell Proliferation
eltrombopag
lenalidomide
Safety
Cell Line
Therapeutics
Growth

Keywords

  • AML
  • Eltrombopag
  • Lenalidomide
  • MDS

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

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title = "Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone",
abstract = "Lenalidomide (Len) is clinically indicated in myelodysplastic syndrome (MDS) but its use is limited by significant thrombocytopenia. Eltrombopag (EP) is a thrombopoietin receptor agonist that can stimulate platelet production and has shown preclinical efficacy in inhibiting leukemic cell proliferation. Thus, we determined the preclinical efficacy and safety of combining Len and EP in acute myelogenous leukemia (AML) and MDS. We found that single agent treatment of leukemia and lymphoma cell lines with EP and Len showed differential sensitivities to either agent. Combination therapy did not result in reversal of anti-malignant effects on these cells. Furthermore, the combination of Len and EP resulted in significant inhibitory effects on growth of leukemic colonies in the majority of primary MDS and AML samples. Most importantly, EP was able to reverse the anti-megakaryopoietic effects of Len in primary MDS patient samples. These results provide a preclinical rationale for the use of this combination in MDS and AML.",
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author = "Roni Tamari and Carolina Schinke and Tushar Bhagat and Michael Roth and Ira Braunschweig and Britta Will and Steidl, {Ulrich G.} and Verma, {Amit K.}",
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T1 - Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone

AU - Tamari, Roni

AU - Schinke, Carolina

AU - Bhagat, Tushar

AU - Roth, Michael

AU - Braunschweig, Ira

AU - Will, Britta

AU - Steidl, Ulrich G.

AU - Verma, Amit K.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Lenalidomide (Len) is clinically indicated in myelodysplastic syndrome (MDS) but its use is limited by significant thrombocytopenia. Eltrombopag (EP) is a thrombopoietin receptor agonist that can stimulate platelet production and has shown preclinical efficacy in inhibiting leukemic cell proliferation. Thus, we determined the preclinical efficacy and safety of combining Len and EP in acute myelogenous leukemia (AML) and MDS. We found that single agent treatment of leukemia and lymphoma cell lines with EP and Len showed differential sensitivities to either agent. Combination therapy did not result in reversal of anti-malignant effects on these cells. Furthermore, the combination of Len and EP resulted in significant inhibitory effects on growth of leukemic colonies in the majority of primary MDS and AML samples. Most importantly, EP was able to reverse the anti-megakaryopoietic effects of Len in primary MDS patient samples. These results provide a preclinical rationale for the use of this combination in MDS and AML.

AB - Lenalidomide (Len) is clinically indicated in myelodysplastic syndrome (MDS) but its use is limited by significant thrombocytopenia. Eltrombopag (EP) is a thrombopoietin receptor agonist that can stimulate platelet production and has shown preclinical efficacy in inhibiting leukemic cell proliferation. Thus, we determined the preclinical efficacy and safety of combining Len and EP in acute myelogenous leukemia (AML) and MDS. We found that single agent treatment of leukemia and lymphoma cell lines with EP and Len showed differential sensitivities to either agent. Combination therapy did not result in reversal of anti-malignant effects on these cells. Furthermore, the combination of Len and EP resulted in significant inhibitory effects on growth of leukemic colonies in the majority of primary MDS and AML samples. Most importantly, EP was able to reverse the anti-megakaryopoietic effects of Len in primary MDS patient samples. These results provide a preclinical rationale for the use of this combination in MDS and AML.

KW - AML

KW - Eltrombopag

KW - Lenalidomide

KW - MDS

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