The multiple ways Wnt signaling contributes to acute leukemia pathogenesis

Abstract

WNT proteins constitute a very conserved family of secreted glycoproteins that act as shortrange ligands for signaling with critical roles in hematopoiesis, embryonic development, and tissue homeostasis. These proteins transduce signals via the canonical pathway, which iscatenin-mediated and better-characterized, or via more diverse noncanonical pathways that are-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 consider

FZD6 triggers Wnt–signalling driven by WNT10BIVS1 expression and highlights new targets in T‐cell acute lymphoblastic leukemia

“…Previous studies have explored the multiple ways abnormal Wnt signaling contributes to the pathogenesis of human leukemia 16,17,26,27,42–45 . Our recent findings also highlight the high prevalence of a WNT10B rearrangement ( WNT10B R ), involving intron 1 proximal to the exon 2, and expressing the WNT10B IVS1 transcript in acute myeloid leukemia with normal karyotype 27 .…”

“…Previous studies have explored the multiple ways abnormal Wnt signaling contributes to the pathogenesis of human leukemia. 16 , 17 , 26 , 27 , 42 , 43 , 44 , 45 Our recent findings also highlight the high prevalence of a WNT10B rearrangement ( WNT10B R ), involving intron 1 proximal to the exon 2, and expressing the WNT10B IVS1 transcript in acute myeloid leukemia with normal karyotype. 27 Based on prior results, it has been suggested the importance of abnormal Wnt activation in T‐ALL patients, supported by patients being characterized by a minor subpopulation of Wnt‐active cells highly enriched for leukemia‐initiating cells (LICs) with both T‐ and myeloid cell potential.…”

“…Recent models highlight the complex nature of Wnt‐mediated gene regulation underlining that β‐catenin is not sufficient for gene target activation (https://web.stanford.edu/group/nusselab/cgi-bin/wnt/target_genes). 14,15 Altered expression levels of Wnt signaling components have been closely related to initiation and progression of acute and chronic leukemia 16–18 . The highest level of active Wnt signaling is detected in the most immature CD4 − CD8 − (double negative, DN) cells by differential expression, which is determined by elevated levels of activating and lower levels of inhibiting factors in the Wnt signaling cascade 19 .…”

“… 14 , 15 Altered expression levels of Wnt signaling components have been closely related to initiation and progression of acute and chronic leukemia. 16 , 17 , 18 The highest level of active Wnt signaling is detected in the most immature CD4 − CD8 − (double negative, DN) cells by differential expression, which is determined by elevated levels of activating and lower levels of inhibiting factors in the Wnt signaling cascade. 19 WNT ligands may also regulate T‐cell mediated immune responses by secreted factors that stimulate bone formation and hemopoietic cells, 20 one of them being WNT10B.…”

Cytoplasmic NEAT1 Suppresses AML Stem Cell Self‐Renewal and Leukemogenesis through Inactivation of Wnt Signaling

“…[8] While accumulating evidence shows the importance of 𝛽-catenin in regulating LSC function, little is known about the role and regulatory mechanism of DVL2 in LSC of AML. [9] Long non-coding RNAs (lncRNAs) play crucial roles in various biological processes such as tumorigenesis. Nuclear paraspeckle assembly transcript 1 (NEAT1) is one of the most well-studied lncRNAs, which contains a short isoform, NEAT1_1 (3.7kb), [10] and a long isoform, NEAT1_2 (23kb).…”