DPP4 truncated GM-CSF and IL-3 manifest distinct receptor-binding and regulatory functions compared with their full-length forms

H. A. O'Leary, M. Capitano, S. Cooper, C. Mantel, H. Boswell, Reuben Kapur, B. Ramdas, Rebecca Chan, L. Deng, C. K. Qu, Hal Broxmeyer

Research output: Contribution to journalArticle

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Abstract

Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony-stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated (T) factors (T-granulocyte-macrophage-CSF (T-GM-CSF)) and T-interleukin-3 (T-IL-3)) on both in vitro and in vivo models of normal and leukemic cells. T-GM-CSF and -IL-3 had enhanced receptor binding, but decreased CSF activity, compared with their FL forms. Importantly, T-GM-CSF and -IL-3 significantly, and reciprocally, blunted receptor binding and myeloid progenitor cell proliferation activity of both FL-GM-CSF and -IL-3 in vitro and in vivo. Similar effects were apparent in vitro using cluster-forming cells from patients with acute myeloid leukemia regardless of cytogenetic or molecular alterations and in vivo using animal models of leukemia. This suggests that DPP4 T-molecules have modified binding and functions compared with their FL counterparts and may serve regulatory roles in normal and malignant hematopoiesis.

Original languageEnglish (US)
Pages (from-to)2468-2478
Number of pages11
JournalLeukemia
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2017

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Colony-Stimulating Factors
Interleukin-3
Hematopoiesis
Granulocytes
Experimental Leukemias
Macrophages
Myeloid Progenitor Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Acute Myeloid Leukemia
Cytogenetics
Blood Cells
Cell Proliferation
Amino Acids
In Vitro Techniques
Proteins

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

DPP4 truncated GM-CSF and IL-3 manifest distinct receptor-binding and regulatory functions compared with their full-length forms. / O'Leary, H. A.; Capitano, M.; Cooper, S.; Mantel, C.; Boswell, H.; Kapur, Reuben; Ramdas, B.; Chan, Rebecca; Deng, L.; Qu, C. K.; Broxmeyer, Hal.

In: Leukemia, Vol. 31, No. 11, 01.11.2017, p. 2468-2478.

Research output: Contribution to journalArticle

O'Leary, H. A. ; Capitano, M. ; Cooper, S. ; Mantel, C. ; Boswell, H. ; Kapur, Reuben ; Ramdas, B. ; Chan, Rebecca ; Deng, L. ; Qu, C. K. ; Broxmeyer, Hal. / DPP4 truncated GM-CSF and IL-3 manifest distinct receptor-binding and regulatory functions compared with their full-length forms. In: Leukemia. 2017 ; Vol. 31, No. 11. pp. 2468-2478.
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