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Booker BE, Clark RS, Pellom ST, et al. Interleukin-34 induces monocytic-like differentiation in leukemia cell lines. Int J Biochem Mol Biol. 2015;6(1):1-16
Booker, B. E., Clark, R. S., Pellom, S. T., & Adunyah, S. E. (2015). Interleukin-34 induces monocytic-like differentiation in leukemia cell lines. International journal of biochemistry and molecular biology, 6(1), 1-16.
Booker, Burthia E, et al. "Interleukin-34 induces monocytic-like differentiation in leukemia cell lines." International journal of biochemistry and molecular biology vol. 6,1 (2015): 1-16.
Booker BE, Clark RS, Pellom ST, Adunyah SE. Interleukin-34 induces monocytic-like differentiation in leukemia cell lines. Int J Biochem Mol Biol. 2015 Mar 20;6(1):1-16. eCollection 2015. PMID: 26045972; PMCID: PMC4443290.
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Int J Biochem Mol Biol. 2015 Mar 20;6(1):1-16. eCollection 2015.

Interleukin-34 induces monocytic-like differentiation in leukemia cell lines.

International journal of biochemistry and molecular biology

Burthia E Booker, Ryan S Clark, Samuel T Pellom, Samuel E Adunyah

Affiliations

  1. Department of Biochemistry and Cancer Biology, Meharry Medical College Nashville, TN., USA 37208.
  2. Department of Pharmacology, Meharry Medical College Nashville, TN., USA 37208.
  3. Department of Microbiology, Meharry Medical College Nashville, TN., USA 37208.

PMID: 26045972 PMCID: PMC4443290

Abstract

Interleukin-34 (IL-34) is a cytokine consisting of a 39kD homodimer, shown to be a ligand for both the Macrophage Colony Stimulating Factor (M-CSF/CSF-1) receptor and the Receptor-like protein tyrosine phosphatase-zeta (RPTP-ƺ). IL-34 has been shown to promote monocyte viability and proliferation as well as the differentiation of bone marrow cells into macrophage progenitors. Published work on IL-34 involves its effects on normal hematopoietic and osteoclast progenitors. However, it is not known whether IL-34 has biologic effects in cancer, including leukemia. Here we report that the biological effects of IL-34 include induction of differential expression of Interleukins-1α and -1β as well as induction of differentiation of U937, HL-60 and THP-1 leukemia cell lines demonstrating monocyte-like characteristics. The ability of IL-34 to induce monocytic-like differentiation is supported by strong morphological and functional evidence. Cell surface markers of myeloid lineage, CD64 and CD86, remain constant while the levels of CD11b and CD71 decline with IL-34 treatment. IL-34 also induced increases in CD14 and CD68 expression, further supporting maturation toward monocytic character. IL-34-induced differentiated U937 and THP-1 cell lines exhibited biological functions such as endocytosis and respiratory burst activities. Collectively, we conclude that while IL-34 does not induce cell growth or proliferation, it is able to induce differentiation of leukemia cell lines from monoblastic precursor cells towards monocyte- and macrophage-like cells, mediated through the JAK/STAT and PI3K/Akt pathways. To our knowledge, this is the first report that IL-34 induces differentiation in human leukemic cells, let alone any cancer model.

Keywords: IL-34; Interleukin-34; JAK/STAT; PI3K/Akt; differentiation; leukemia

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