Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review

Charan Thej Reddy Vegivinti, Praneeth Reddy Keesari, Sindhusha Veeraballi, Catarina Maria Pina Martins Maia, Ansh Krishnachandra Mehta, Rohit Reddy Lavu, Rahul Kumar Thakur, Sri Harsha Tella, Riya Patel, Venkata Kiranmayi Kakumani, Yashwitha Sai Pulakurthi, Srinivas Aluri, Ritesh Kumar Aggarwal, Nandini Ramachandra, Rongbao Zhao, Srabani Sahu, Aditi Shastri, Amit Verma

Research output: Contribution to journalReview articlepeer-review

Abstract

Dysregulation of the innate immune system and inflammatory-related pathways has been implicated in hematopoietic defects in the bone marrow microenvironment and associated with aging, clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). As the innate immune system and its pathway regulators have been implicated in the pathogenesis of MDS/AML, novel approaches targeting these pathways have shown promising results. Variability in expression of Toll like receptors (TLRs), abnormal levels of MyD88 and subsequent activation of NF-κβ, dysregulated IL1-receptor associated kinases (IRAK), alterations in TGF-β and SMAD signaling, high levels of S100A8/A9 have all been implicated in pathogenesis of MDS/AML. In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic targets from recent clinical trials including the use of monoclonal antibodies and small molecule inhibitors against these pathways.

Original languageEnglish (US)
Article number60
JournalExperimental Hematology and Oncology
Volume12
Issue number1
DOIs
StatePublished - Dec 2023

Keywords

  • Acute myeloid leukemia (AML)
  • IL1 receptor Associated kinase (IRAK)
  • Inflammasome
  • Innate Immune pathways
  • Myelodysplastic syndromes (MDS)
  • Toll like receptors (TLRs)
  • Tumor microenvironment (TME)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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