Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts

Meir Wetzler, Steven H. Bernstein, Heinz Baumann, Kristin M. Fries, Carleton Stewart, Leslie Blumenson, Maria R. Baer, Geoffrey P. Herzig, Clara D. Bloomfield, James L Slack

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The receptor for megakaryocyte growth and development factor (MGDF), also known as thrombopoietin, has recently been cloned. MGDF stimulates platelet production and maturation both in vitro and in vivo. MGDF may thus have a role in attenuating the thrombocytopenia associated with acute myeloid leukemia (AML) and its therapy. However, there is concern that MGDF might induce AML blast proliferation and thereby increase the risk of treatment failure. To address this concern, we studied the expression of c-mpl mRNA and c-Mpl protein by blasts from AML patients. In addition we examined the in vitro effect of MGDF as well as the combined effect of MGDF and granulocyte colony-stimulating factor (G-CSF) or stem cell factor (SCF) on leukemic blast proliferation, recruitment into S-phase, induction of programmed cell death and activation of signal transducers and activators of transcription (STAT) proteins. Our results demonstrate that blasts from a substantial proportion of cases of AML express the receptor at either the mRNA or protein level. Moreover, the function of the MGDF receptor was demonstrated by activation of STAT proteins following exposure to MGDF. Nevertheless, blast proliferation in response to MGDF was rare, and the proliferative effect of MGDF was less than that of G-CSF or SCF. Furthermore, MGDF did not prevent programmed cell death induced by cytarabine. Finally, there appeared to be no correlation between receptor expression by AML blasts and functional response to MGDF. Based on these data, it would appear that clinical trials of MGDF may be undertaken safely in patients with AML.

Original languageEnglish (US)
Pages (from-to)415-431
Number of pages17
JournalLeukemia and Lymphoma
Volume30
Issue number5-6
StatePublished - 1998
Externally publishedYes

Fingerprint

Thrombopoietin
Growth Factor Receptors
Acute Myeloid Leukemia
STAT Transcription Factors
Stem Cell Factor
Granulocyte Colony-Stimulating Factor
Core Binding Factor alpha Subunits
Cell Death
Messenger RNA
Cytarabine
Treatment Failure
S Phase
Thrombocytopenia

Keywords

  • Acute myeloid leukemia blasts
  • AML
  • Function
  • Megakaryocyte growth and development factor
  • MGDF
  • MGDF receptor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Wetzler, M., Bernstein, S. H., Baumann, H., Fries, K. M., Stewart, C., Blumenson, L., ... Slack, J. L. (1998). Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts. Leukemia and Lymphoma, 30(5-6), 415-431.

Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts. / Wetzler, Meir; Bernstein, Steven H.; Baumann, Heinz; Fries, Kristin M.; Stewart, Carleton; Blumenson, Leslie; Baer, Maria R.; Herzig, Geoffrey P.; Bloomfield, Clara D.; Slack, James L.

In: Leukemia and Lymphoma, Vol. 30, No. 5-6, 1998, p. 415-431.

Research output: Contribution to journalArticle

Wetzler, M, Bernstein, SH, Baumann, H, Fries, KM, Stewart, C, Blumenson, L, Baer, MR, Herzig, GP, Bloomfield, CD & Slack, JL 1998, 'Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts', Leukemia and Lymphoma, vol. 30, no. 5-6, pp. 415-431.
Wetzler M, Bernstein SH, Baumann H, Fries KM, Stewart C, Blumenson L et al. Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts. Leukemia and Lymphoma. 1998;30(5-6):415-431.
Wetzler, Meir ; Bernstein, Steven H. ; Baumann, Heinz ; Fries, Kristin M. ; Stewart, Carleton ; Blumenson, Leslie ; Baer, Maria R. ; Herzig, Geoffrey P. ; Bloomfield, Clara D. ; Slack, James L. / Expression and function of the megakaryocyte growth and development factor receptor in acute myeloid leukemia blasts. In: Leukemia and Lymphoma. 1998 ; Vol. 30, No. 5-6. pp. 415-431.
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AU - Stewart, Carleton

AU - Blumenson, Leslie

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