Direct inhibition of human acute myeloid leukemia cell growth by IL-12

Elisa Ferretti, Emma Di Carlo, Claudia Cocco, Domenico Ribatti, Carlo Sorrentino, Emanuela Ognio, Daniela Montagna, Vito Pistoia, Irma Airoldi

Research output: Contribution to journalArticle

Abstract

Acute myeloid leukemia is a haematopoietic malignancy originating from the transformation of myeloid progenitors that proliferate and accumulate in the bone marrow. In AML patients the survival rate at 5 years is 40-50% highlighting the need for novel therapies. In this study we have asked whether IL-12, an immuno-modulatory cytokine with anti-tumor activity, may inhibit directly AML cell growth. We show that the human AML cell lines U937, K562 and THP-1 expressed both chains of the IL-12 receptor (R), i.e. IL-12Rβ1 and IL-12Rβ2. IL-12 inhibited the angiogenic potential of AML cells in vitro, but did not affect their survival or proliferation. In vivo experiments were performed using SCID-NOD mice injected intraperitoneally (i.p.) with the human U937 AML cell line and subsequently treated with human recombinant IL-12 or PBS i.p. Histological, immunohistochemical and flow cytometric analyses on explanted tumors revealed that IL-12 reduced new vessel formation, induced apoptosis and inhibited tumor cell proliferation. Studies on a panel of angiogenesis related genes in explanted tumors using PCR arrays showed significantly down-regulated expression of numerous pro-angiogenic genes including VEGF-C, IL-6, IL-8, CXCL1, CXCL6 and alanyl aminopeptidase in IL-12 vs PBS treated mice. This study shows for the first time that IL-12 targets directly AML cell growth and paves the way to further investigation of IL-12 as potential drug for AML treatment.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalImmunology Letters
Volume133
Issue number2
DOIs
Publication statusPublished - Oct 2010

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Myeloid Cells
Interleukin-12
Acute Myeloid Leukemia
Growth
Neoplasms
Interleukin-12 Receptors
Vascular Endothelial Growth Factor C
CD13 Antigens
Cell Line
U937 Cells
Inbred NOD Mouse
SCID Mice
Hematologic Neoplasms
Interleukin-8
Genes
Interleukin-6
Survival Rate
Bone Marrow
Cell Proliferation
Apoptosis

Keywords

  • AML
  • IL-12
  • IL-12R

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Ferretti, E., Di Carlo, E., Cocco, C., Ribatti, D., Sorrentino, C., Ognio, E., ... Airoldi, I. (2010). Direct inhibition of human acute myeloid leukemia cell growth by IL-12. Immunology Letters, 133(2), 99-105. https://doi.org/10.1016/j.imlet.2010.08.002

Direct inhibition of human acute myeloid leukemia cell growth by IL-12. / Ferretti, Elisa; Di Carlo, Emma; Cocco, Claudia; Ribatti, Domenico; Sorrentino, Carlo; Ognio, Emanuela; Montagna, Daniela; Pistoia, Vito; Airoldi, Irma.

In: Immunology Letters, Vol. 133, No. 2, 10.2010, p. 99-105.

Research output: Contribution to journalArticle

Ferretti, E, Di Carlo, E, Cocco, C, Ribatti, D, Sorrentino, C, Ognio, E, Montagna, D, Pistoia, V & Airoldi, I 2010, 'Direct inhibition of human acute myeloid leukemia cell growth by IL-12', Immunology Letters, vol. 133, no. 2, pp. 99-105. https://doi.org/10.1016/j.imlet.2010.08.002
Ferretti E, Di Carlo E, Cocco C, Ribatti D, Sorrentino C, Ognio E et al. Direct inhibition of human acute myeloid leukemia cell growth by IL-12. Immunology Letters. 2010 Oct;133(2):99-105. https://doi.org/10.1016/j.imlet.2010.08.002
Ferretti, Elisa ; Di Carlo, Emma ; Cocco, Claudia ; Ribatti, Domenico ; Sorrentino, Carlo ; Ognio, Emanuela ; Montagna, Daniela ; Pistoia, Vito ; Airoldi, Irma. / Direct inhibition of human acute myeloid leukemia cell growth by IL-12. In: Immunology Letters. 2010 ; Vol. 133, No. 2. pp. 99-105.
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