Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia

M. R. Ricciardi, T. McQueen, D. Chism, M. Milella, E. Estey, E. Kaldjian, J. Sebolt-Leopold, M. Konopleva, M. Andreeff

Research output: Contribution to journalArticle

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Abstract

We investigated the constitutive activation of the MEK/ERK pathway in acute myelogenous leukemia (AML) via a flow cytometric technique to quantitate expression of phosphorylated ERK (p-ERK). A total of 42 AML samples (16 newly diagnosed, 26 relapsed/refractory) were analyzed. Normal bone marrow CD34+ cells (n =10) had little or no expression of p-ERK, while G-CSF-mobilized CD34+ cells exhibited enhanced p-ERK levels. Markedly elevated p-ERK levels were found in 83.3% of the AML samples, with no differences observed between the newly diagnosed and relapsed/refractory samples. Treatment with a MEK inhibitor resulted in significantly decreased p-ERK levels in both the newly diagnosed and relapsed/refractory samples, which was associated with growth arrest, but not apoptosis induction. In summary, we defined conditions for the analysis of MAPK signaling in primary AML samples. Normal CD34+ cells expressed very low levels of p-ERK, and increased p-ERK levels were found in normal G-CSF-stimulated circulating CD34+ cells. Constitutively high p-ERK levels observed in the majority of AML samples suggest deregulation of this pathway that appears to be independent of disease status. The ability of ERK inhibition to promote growth arrest rather than apoptosis suggests that clinical trials of MEK/ERK inhibitors may be more effective when combined with chemotherapy.

Original languageEnglish
Pages (from-to)1543-1549
Number of pages7
JournalLeukemia
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Acute Myeloid Leukemia
Phosphorylation
Mitogen-Activated Protein Kinase Kinases
Granulocyte Colony-Stimulating Factor
Apoptosis
MAP Kinase Signaling System
Growth
Bone Marrow Cells
Clinical Trials
Drug Therapy
Therapeutics

Keywords

  • Acute myelogenous leukemia
  • ERK
  • G-CSF
  • Hematopoietic progenitor cells
  • MEK/ERK inhibitors

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia. / Ricciardi, M. R.; McQueen, T.; Chism, D.; Milella, M.; Estey, E.; Kaldjian, E.; Sebolt-Leopold, J.; Konopleva, M.; Andreeff, M.

In: Leukemia, Vol. 19, No. 9, 09.2005, p. 1543-1549.

Research output: Contribution to journalArticle

Ricciardi, MR, McQueen, T, Chism, D, Milella, M, Estey, E, Kaldjian, E, Sebolt-Leopold, J, Konopleva, M & Andreeff, M 2005, 'Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia', Leukemia, vol. 19, no. 9, pp. 1543-1549. https://doi.org/10.1038/sj.leu.2403859
Ricciardi, M. R. ; McQueen, T. ; Chism, D. ; Milella, M. ; Estey, E. ; Kaldjian, E. ; Sebolt-Leopold, J. ; Konopleva, M. ; Andreeff, M. / Quantitative single cell determination of ERK phosphorylation and regulation in relapsed and refractory primary acute myeloid leukemia. In: Leukemia. 2005 ; Vol. 19, No. 9. pp. 1543-1549.
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