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.

中文翻译：

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Wnt信号传导的多种方式有助于急性白血病的发病机理。

WNT蛋白是一个非常保守的分泌糖蛋白家族，可作为短程配体，在造血，胚胎发育和组织动态平衡中起关键作用。这些蛋白质通过β-catenin介导且更好地表征的经典途径，或通过β-catenin独立且包含平面细胞极性（PCP）途径和WNT / Ca ^++的更多样化的非经典途径来转导信号。途径。几种蛋白质通过多种复杂的机制调节Wnt信号传导。该途径内的疾病可导致多种人类疾病，并且通过不同分子机制引起的Wnt途径失调与包括血液系统恶性肿瘤在内的许多类型癌症的发病机理有关。白血病的类型差异很大，根据主要细胞的分化阶段，祖细胞谱系，诊断年龄层和特定的分子驱动因素，可分为慢性，髓样或淋巴细胞性和急性，髓样或淋巴细胞性白血病。他们发展的背后。在这里，我们回顾了Wnt信号在正常造血中的作用，并详细讨论了规范性Wnt信号在急性白血病中失调的多种方式，包括基因表达和蛋白质水平的变化，表观遗传调控和突变。此外，考虑到疾病的不同形式以及靶向Wnt信号的治疗潜力，我们强调了这些改变的不同影响。