Chronic Myeloid Leukemia Coverage from Every Angle
Advertisement
Advertisement

Research Sheds Light on Plasmacytoid Dendritic Cells in CML

By: Melissa E. Fryman, MS
Posted: Thursday, February 21, 2019

Plasmacytoid dendritic cells in patients with chronic myeloid leukemia (CML) have been heretofore not well understood. According to results from a study by Andreas Burchert, MD, of the Philipps University of Marburg, Germany, and colleagues, the function of these cells may be multifold. Of note, the authors wrote, “qualitative (activation of plasmacytoid dendritic cells and BCR-ABL status) and quantitative (high versus low plasmacytoid dendritic cell counts) factors govern the outcome of [plasmacytoid dendritic cells]-biology in CML, which can be tumor-suppressive or -promoting.” Results from their study were published in Cancer Research.

“We find that CML-[plasmacytoid dendritic cells] emerge from low-level BCR-ABL–positive stem cells, produce inflammatory cytokines, and retain important functional properties, such as [interferon] secretion, maturation, and elicitation of CML-specific immunity,” the authors concluded.

Several lines of experimentation, using mouse transduction/transplantation-CML models and human blood samples, were used in this study. Contrary to previous reports, plasmacytoid dendritic cell counts were not lowered due to BCR-ABL–induced suppression of IRF8. Compared with normal donor plasmacytoid dendritic cells, gene-expression profiles of these cells showed 3,109 differentially regulated genes, of which enrichment in several genes related to innate and adaptive immunity was noted. CML–plasmacytoid dendritic cells overexpressed inflammatory cytokines and were frequently spontaneously activated, compared with normal donor plasmacytoid dendritic cells .

Development of CML–plasmacytoid dendritic cells could be blocked by in vivo treatment with the BCR-ABL–specific tyrosine kinase inhibitor nilotinib, which the authors wrote may lead to reduced plasmacytoid dendritic cell levels during molecular remission. However, due to detectable BCR-ABL–positive CML–plasmacytoid dendritic cells in all patient samples, “even in very deep molecular remission of CML,” the authors concluded that some of these cells are likely insensitive to tyrosine kinase inhibitors, possibly due to immune escape.

“Further studies are warranted to eventually exploit oncogene-expressing [plasmacytoid dendritic cells] as leukemia vaccines,” concluded the authors.

Disclosure: The study authors’ disclosure information may be found at aacrjournals.org.



By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.