Abstract 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.
WANG Wen-Peng,GUO Lei,LI Yan et al. Expression and significance of dishevelled proteins in the Wnt pathway in childhood acute lymphoblastic leukemia[J]. CJCP, 2019, 21(5): 411-414.
WANG Wen-Peng,GUO Lei,LI Yan et al. Expression and significance of dishevelled proteins in the Wnt pathway in childhood acute lymphoblastic leukemia[J]. CJCP, 2019, 21(5): 411-414.
Stary J, Zimmermann M, Campbell M, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia:results of the randomized intercontinental trial ALL IC-BFM 2002[J]. J Clin Oncol, 2014, 32(3):174-184.
[3]
Chang B, Tessneer KL, McManus J, et al. Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development[J]. Nat Commun, 2015, 6:6380.
[4]
Castro-Piedras I, Sharma M, den Bakker M, et al. DVL1 and DVL3 differentially localize to CYP19A1 promoters and regulate aromatase mRNA in breast cancer cells[J]. Oncotarget, 2018, 9(86):35639-35654.
[5]
Çalışkan C, Pehlivan M, Yüce Z. Dishevelled proteins and CYLD reciprocally regulate each other in CML cell lines[J]. Mol Biol Rep, 2017, 44(5):391-397.
Katoh M. Canonical and non-canonical WNT signaling in cancer stem cells and their niches:cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review)[J]. Int J Oncol, 2017, 51(5):1357-1369.
[9]
Thiago LS, Costa ES, Lopes DV, et al. The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance[J]. Biomed Pharmacother, 2010, 64(1):63-72.
[10]
Janovská P. Wnt signalling pathways in chronic lymphocytic leukaemia and B-cell lymphomas[J]. Br J Pharmacol, 2017, 174(24):4701-4715.
[11]
Sharma M, Castro-Piedras I, Simmons GE. Dishevelled:a masterful conductor of complex Wnt signals[J]. Cell Signal, 2018, 47:52-64.
[12]
Tauriello DV, Jordens I, Kirchner K, et al. Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled[J]. Proc Natl Acad Sci U S A, 2012, 109(14):E812-E820.
[13]
Bienz M. Signalosome assembly by domains undergoing dynamic head-to-tail polymerization[J]. Trends Biochem Sci, 2014, 39(10):487-495.
[14]
Wang W, Li X, Lee M, et al. FOXKs promote Wnt/β-catenin signaling by translocating DVL into the nucleus[J]. Dev Cell, 2015, 32(6):707-718.
[15]
Li J, Guo G, Li J, et al. The expression and significance of dishevelled in human glioma[J]. J Surg Res, 2014, 192(2):509-514.
van der Veer A, Zaliova M, Mottadelli F, et al. IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL[J]. Blood, 2014, 123(11):1691-1698.
[20]
Fischer U, Forster M, Rinaldi A, et al. Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options[J]. Nat Genet, 2015, 47(9):1020-1029.
[21]
Gu Z, Churchman M, Roberts K, et al. Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia[J]. Nat Commun, 2016, 7:13331.