[Expression and significance of dishevelled proteins in the Wnt pathway in childhood acute lymphoblastic leukemia].

OBJECTIVE To study the significance of dishevelled (DVL) proteins in the Wnt signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL). METHODS A total of 33 children with new-onset ALL were enrolled as the case group. According to the degree of risk, they were divided into 3 groups: low-risk (n=14), intermediate-risk (n=5) and high-risk (n=14). A total of 29 children with immune thrombocytopenia were enrolled as the control group. At diagnosis and on day 33 of induction therapy, 2 mL bone marrow samples were collected from the case and control groups, and qRT-PCR was used to measure the mRNA expression of DVL1, DVL2 and DVL3 in blood cells of bone marrow. RESULTS The mRNA expression of DVL1, DVL2 and DVL3 in the case group in the incipient stage was significantly higher than that in the remission stage and the control group (P<0.05). Compared with the control group, the case group had a significant increase in the mRNA expression of DVL2 in the remission stage (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in both remission and incipient stages (P<0.05). The high- and intermediate-risk groups had significantly higher mRNA expression of DVL1 and DVL2 than the low-risk group (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in the low-, intermediate- and high-risk groups (P<0.05). CONCLUSIONS The change in the expression of DVL, especially DVL2, in the Wnt signal pathway has certain significance in the pathogenesis and prognosis of childhood ALL.

[1]  K. Pruitt,et al.  DVL1 and DVL3 differentially localize to CYP19A1 promoters and regulate aromatase mRNA in breast cancer cells , 2018, Oncotarget.

[2]  Glenn E. Simmons,et al.  Dishevelled: A masterful conductor of complex Wnt signals. , 2018, Cellular signalling.

[3]  M. Katoh.  Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review) , 2017, International journal of oncology.

[4]  M. Pehlivan,et al.  Dishevelled proteins and CYLD reciprocally regulate each other in CML cell lines , 2017, Molecular Biology Reports.

[5]  V. Bryja,et al.  Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas , 2017, British journal of pharmacology.

[6]  Guido Marcucci,et al.  Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia , 2016, Nature Communications.

[7]  Thomas Zichner,et al.  Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options , 2015, Nature Genetics.

[8]  Moonsup Lee,et al.  FOXKs promote Wnt/β-catenin signaling by translocating DVL into the nucleus. , 2015, Developmental cell.

[9]  Hao Wu,et al.  Epsin is required for Dishevelled stability and Wnt signaling activation in colon cancer development , 2015, Nature Communications.

[10]  Jianjun Zhang,et al.  The expression and significance of dishevelled in human glioma. , 2014, The Journal of surgical research.

[11]  M. Bienz.  Signalosome assembly by domains undergoing dynamic head-to-tail polymerization. , 2014, Trends in biochemical sciences.

[12]  M. D. Den Boer,et al.  IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL. , 2014, Blood.

[13]  O. Hrusak,et al.  Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Britta A. M. Bouwman,et al.  Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled , 2012, Proceedings of the National Academy of Sciences.

[15]  Ye Guang Chen,et al.  Dishevelled: The hub of Wnt signaling. , 2010, Cellular signalling.

[16]  K. Pruitt,et al.  DVL1 and DVL3 differentially localize to CYP19A1 promoters and regulate aromatase mRNA in breast cancer cells , 2018, Oncotarget.

[17]  A. Órfão,et al.  The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance. , 2010, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.