A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone

Joaquin J. Jimenez, Gina M. Delcanto, Petra Popovics, Aymee Perez, Ailin Vila Granda, Irving Vidaurre, Ren Zhi Cai, Ferenc G. Rick, Ronan T Swords, Andrew V. Schally

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and acts on the pituitary gland to stimulate the release of growth hormone (GH). GHRH can also be produced by human cancers, in which it functions as an autocrine/paracrine growth factor. We have previously shown that synthetic antagonistic analogues of GHRH are able to successfully suppress the growth of 60 different human cancer cell lines representing over 20 cancers. Nevertheless, the expression of GHRH and its receptors in leukaemias has never been examined. Our study demonstrates the presence of GHRH receptor (GHRH-R) on 3 of 4 human acute myeloid leukaemia (AML) cell lines-K-562, THP-1, and KG-1a-and significant inhibition of proliferation of these three cell lines in vitro following incubation with the GHRH antagonist MIA-602. We further show that this inhibition of proliferation is associated with the upregulation of pro-apoptotic genes and inhibition of Akt signalling in leukaemic cells. Treatment with MIA-602 of mice bearing xenografts of these human AML cell lines drastically reduced tumour growth. The expression of GHRH-R was further confirmed in 9 of 9 samples from patients with AML. These findings offer a new therapeutic approach to this malignancy and suggest a possible role of GHRH-R signalling in the pathology of AML.

Original languageEnglish (US)
JournalBritish Journal of Haematology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Growth Hormone-Releasing Hormone
Acute Myeloid Leukemia
Cell Line
Myeloid Cells
Neoplasms
Therapeutics
Hormone Antagonists
Pituitary Gland
Growth
Heterografts
Growth Hormone
Hypothalamus
somatotropin releasing hormone receptor
Intercellular Signaling Peptides and Proteins
Leukemia
Up-Regulation
Pathology
Genes

Keywords

  • Acute myeloid leukaemia
  • Antagonist
  • Growth hormone-releasing hormone
  • Hormone
  • Leukaemia

ASJC Scopus subject areas

  • Hematology

Cite this

A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone. / Jimenez, Joaquin J.; Delcanto, Gina M.; Popovics, Petra; Perez, Aymee; Vila Granda, Ailin; Vidaurre, Irving; Cai, Ren Zhi; Rick, Ferenc G.; Swords, Ronan T; Schally, Andrew V.

In: British Journal of Haematology, 01.01.2018.

Research output: Contribution to journalArticle

Jimenez, Joaquin J. ; Delcanto, Gina M. ; Popovics, Petra ; Perez, Aymee ; Vila Granda, Ailin ; Vidaurre, Irving ; Cai, Ren Zhi ; Rick, Ferenc G. ; Swords, Ronan T ; Schally, Andrew V. / A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone. In: British Journal of Haematology. 2018.
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