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The multiple ways Wnt signaling contributes to acute leukemia pathogenesis
Author(s) -
SoaresLima Sheila C.,
PombodeOliveira Maria S.,
Carneiro Flávia R. G.
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2mr0420-707r
Subject(s) - wnt signaling pathway , biology , signal transduction , myeloid leukemia , epigenetics , haematopoiesis , lrp6 , microbiology and biotechnology , leukemia , progenitor cell , myeloid , cancer research , immunology , stem cell , genetics , gene
WNT proteins constitute a very conserved family of secreted glycoproteins that act as short‐range ligands for signaling with critical roles in hematopoiesis, embryonic development, and tissue homeostasis. These proteins transduce signals via the canonical pathway, which is β‐catenin‐mediated and better‐characterized, or via more diverse noncanonical pathways that are β‐catenin independent and comprise the planar cell polarity (PCP) pathway and the WNT/Ca ++ pathways. Several proteins regulate Wnt signaling through a variety of sophisticated mechanisms. Disorders within the pathway can contribute to various human diseases, and the dysregulation of Wnt pathways by different molecular mechanisms is implicated in the pathogenesis of many types of cancer, including the hematological malignancies. The types of leukemia differ considerably and can be subdivided into chronic, myeloid or lymphocytic, and acute, myeloid or lymphocytic, leukemia, according to the differentiation stage of the predominant cells, the progenitor lineage, the diagnostic age strata, and the specific molecular drivers behind their development. Here, we review the role of Wnt signaling in normal hematopoiesis and discuss in detail the multiple ways canonical Wnt signaling can be dysregulated in acute leukemia, including alterations in gene expression and protein levels, epigenetic regulation, and mutations. Furthermore, we highlight the different impacts of these alterations, considering the distinct forms of the disease, and the therapeutic potential of targeting Wnt signaling.