Background: Myeloid neoplasms are a diverse group of malignant diseases with
different entities and numerous patho-clinical features. They arise from mutated clones of
hematopoietic stem- and progenitor cells which expand by outperforming their normal counterparts.
The intracellular signaling profile of cancer cells is the sum of genetic, epigenetic
and microenvironmental influences, and the multiple interconnections between different signaling
pathways make pharmacological targeting complicated.
Objective: To present an overview of known somatic mutations in myeloproliferative neoplasms
(MPN), myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and
the inflammatory signaling pathways affected by them, as well as current efforts to therapeutically
modulate this aberrant inflammatory signaling.
Methods: In this review, we extensively reviewed and compiled salient information with
ClinicalTrials.gov as our source on ongoing studies, and PubMed as our authentic bibliographic
source, using a focused review question.
Results: Mutations affecting immune signal transduction are present to varying extents in
clonal myeloid diseases. While MPN are dominated by a few common mutations, a multitude
of different genes can be mutated in MDS and AML. Mutations can also occur in asymptomatic
persons, a finding called clonal hematopoiesis of indeterminate potential (CHIP). Mutations
in FLT3, JAK, STAT, CBL and RAS can lead to aberrant immune signaling. Protein
kinase inhibitors are entering the clinic and are extensively investigated in clinical trials in
MPN, MDS and AML.
Conclusion: In summary, this article summarizes recent research on aberrant inflammatory
signaling in clonal myeloid diseases and the clinical therapeutic potential of modulation of
signal transduction and effector proteins in the affected pathways.