The role of β-catenin in chronic myeloproliferative disorders

Jauregui, Monica P.; Sanchez, Steven R.; Ewton, April A.; Rice, Lawrence; Perkins, Sherrie L.; Dunphy, Cherie H.; Chang, Chung Che

doi:10.1016/j.humpath.2008.02.007

Cited by 9 publications

(12 citation statements)

References 27 publications

(31 reference statements)

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“…[7][8][9][10][11] Prolonged WNT/β-catenin stimulus, on the other hand, may prevent HSCs from their ability to repopulate and differentiate properly, which may ultimately lead to bone marrow failure [12]. WNT signaling may also predispose to bone marrow pathology; it is dysregulated in myeloproliferative neoplasms and disorders [13,14] and communicates with other bone marrow pathology -related factors, such as transforming growth factor beta (TGF-β) [15]. The exact role of WNT signaling, the key WNT ligands, and the coactivators or inhibitors participating in hematopoietic homeostasis, however, remain yet to be established.…”

Section: Introductionmentioning

confidence: 99%

Defective WNT signaling associates with bone marrow fibrosis—a cross-sectional cohort study in a family with WNT1 osteoporosis

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Defective WNT signaling associates with bone marrow fibrosis—a cross-sectional cohort study in a family with WNT1 osteoporosis

et al. 2017

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“…Alteration of the Wnt/β-catenin pathway also contributes to the etiology of several human cancers, including malignant blood disorders (Deshpande and Buske, 2007; Jauregui et al, 2008; Reya and Clevers, 2005). Wg/Wnt signaling begins through its binding to one or more of its receptors, Frizzled (Fz) and Drosophila Frizzled 2 (DFz2).…”

Section: Introductionmentioning

confidence: 99%

Dual Role of Wingless Signaling in Stem-like Hematopoietic Precursor Maintenance in Drosophila

et al. 2009

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In Drosophila, blood development occurs in a specialized larval hematopoietic organ, the lymph gland (LG), within which stem-like hemocyte precursors or prohemocytes differentiate to multiple blood cell types. Here we show that components of the Wingless (Wg) signaling pathway are expressed in prohemocytes. Loss and gain of function analysis indicates that canonical Wg signaling is required for maintenance of prohemocytes and negatively regulates their differentiation. Wg signals locally in a short range fashion within different compartments of the LG. In addition, Wg signaling positively regulates the proliferation and maintenance of cells that function as a hematopoietic niche in Drosophila, the Posterior Signaling Center (PSC), and in the proliferation of crystal cells. Our studies reveal a conserved function of Wg signaling in the maintenance of stem-like blood progenitors and reveal an involvement of this pathway in the regulation of hemocyte differentiation through its action in the hematopoietic niche.

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“…Because accumulation of β-catenin in the nucleus has been identified in chronic and acute leukemia (37,38), we investigated the effect of β-catenin accumulation on PHB expression. We monitored the expression levels of PHB with lithium chloride (LiCl) treatment, which blocks GSK-3β activity and ultimately affects β-catenin accumulation (39).…”

Section: Resultsmentioning

confidence: 99%

β-catenin induces expression of prohibitin gene in acute leukemic cells

et al. 2017

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Prohibitin (PHB) is a multifunctional protein conserved in eukaryotic systems and shows various expression levels in tumor cells. However, regulation of PHB is not clearly understood. Here, we focused on the regulation of PHB expression by Wnt signaling, one of dominant regulatory signals in various leukemic cells. High mRNA levels of PHB were found in half of clinical leukemia samples. PHB expression was increased by inhibition of the MAPK pathway and decreased by activation of EGF signal. Although cell proliferating signals downregulated the transcription of PHB, treatment with lithium chloride, an analog of the Wnt signal, induced PHB level in various cell types. We identified the TCF-4/LEF-1 binding motif, CATCTG, in the promoter region of PHB by site-directed mutagenesis and ChIP assay. This β-catenin-mediated activation of PHB expression was independent of c-MYC activation, a product of Wnt signaling. These data indicate that PHB is a direct target of β-catenin and the increased level of PHB in leukemia can be regulated by Wnt signaling.

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The role of β-catenin in chronic myeloproliferative disorders

Cited by 9 publications

References 27 publications

Defective WNT signaling associates with bone marrow fibrosis—a cross-sectional cohort study in a family with WNT1 osteoporosis

Defective WNT signaling associates with bone marrow fibrosis—a cross-sectional cohort study in a family with WNT1 osteoporosis

Dual Role of Wingless Signaling in Stem-like Hematopoietic Precursor Maintenance in Drosophila

β-catenin induces expression of prohibitin gene in acute leukemic cells

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