Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy

Zhang, Longhui; Cao, Yang; Dai, Xiangpeng

doi:10.3389/fphar.2022.1065029

Cited by 6 publications

(3 citation statements)

References 104 publications

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“…Deletion or down-regulation of DOCK8 was detected in leukemia, lung cancer, renal cell carcinoma, low-grade gliomas and childhood hairy cell astrocytoma. It has been shown that DOCK8 promotes the mesenchymal-type movement of hepatocellular carcinoma (HCC) cells, and the expression of DOCK8 is negatively correlated with the occurrence of HCC [25]. In our patient cohort, DOCK8 deletions and duplications were not associated with adverse events according to statistical analysis (Figure 6).…”

Section: Discussionmentioning

confidence: 69%

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved

Risinskaya,

Gladysheva,

Abdulpatakhov

et al. 2023

IJMS

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The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort.

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Section: Discussionmentioning

confidence: 69%

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved

Risinskaya,

Gladysheva,

Abdulpatakhov

et al. 2023

IJMS

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“…The dedicator of cytokinesis 8 (DOCK8), a well-studied member of the DOCK protein family, was an atypical guanine nucleotide exchange factor (GEF). DOCK8 has been reported mainly expressed in the immune system, kidney, lung, placenta, pancreas, and microglia of the central nervous system (CNS) (Zhang et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Shu

et al. 2023

Preprint

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It was found that ischemic stroke (IS) was associated with abnormal platelet activity and thrombosis. However, the potential significance of platelet-related genes (PRGs) in IS still needs to be more thorough. This study extracted IS-related transcriptome datasets from the Gene Expression Omnibus (GEO) database. The target genes were obtained by intersecting the differentially expressed genes (DEGs), the module genes related to IS, and PRGs, where the key genes of IS were screened by two machine learning algorithms. The key genes-based diagnostic model was constructed. Gene set enrichment analysis (GSEA) and the immune microenvironment analyses were analyzed targeting key genes in IS. The co-expression, TF-mRNA, and competitive endogenous RNAs (ceRNA) regulatory networks were constructed to reveal the potential regulation of key genes. Potential drugs targeting key genes were predicted as well. Totals of eight target genes were obtained and were associated with immune-related functions. Four platelet-related key genes were acquired, which were related to immunity and energy metabolism. The abnormal expressions of DOCK8, GIMAP5, ICOS were determined by the quantitative real-time Polymerase Chain Reaction (qRT-PCR), and the significant correlations among these key genes were identified. Notably, hsa-miR-17-3p, hsa-miR-3158-3p, hsa-miR-423-3p, and hsa-miR-193a-8p could regulate all key genes at the same time. In addition, Caffeine, Carboplatin, and Vopratelimab were the targeted drugs of these key genes. This study identified four platelet-related key genes of IS, which might help to deepen the understanding of the role of platelet-related genes in the molecular mechanism of IS.

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“…Haploidentical HSCT with post-transplant cyclophosphamide has also been shown to have an emerging role in these children [30]. Future studies are focussing on improving outcome with possible nanotechnology in HSCT for these disorders [31].…”

Section: Discussionmentioning

confidence: 99%

Emerging spectrum of DOCK8 deficiency in children and challenges associated with providing treatment: experience from a tertiary referral centre in India

ganesan,

duraisamy,

nair

et al. 2023

Preprint

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The study describes the course of children with DOCK8 deficiency, their stormy clinical course, discrete infection pattern, and challenges during the treatment. The retrospective study included children up to 18 years of age diagnosed to have genetically proven DOCK8 deficiency from January 2013 to January 2023. A total of nine children were included, with a median age of five years. Clinical presentations included eczema (2/9), viral infections (4/9), recurrent sinopulmonary infections (3/9), impetigo (2/9), autoimmune hemolytic anemia (1/9) and Epstein-Barr virus driven malignancy (1/9). Other infections noted were molluscum contagiosum in two children, cytomegalovirus colitis in one child, and recurrent Klebsiella pneumoniae meningitis. The outcomes of hematopoietic stem cell transplantation (HSCT) remained poor (n=5, three haploidentical HSCT, one each matched family and unrelated donor HSCT), due to early and refractory viral reactivation, with 17,00,000 copies of cytomegalovirus in one child and 8,53,95,600 copies of adenovirus in another child. Secondary late graft failure was noted in one child, two years following a matched sibling donor HSCT. The one who underwent a matched unrelated donor HSCT was doing well and was infection free. The clinical course without HSCT had been stormy, as seen in a child with Burkitt's lymphoma, who succumbed to refractory cytomegaloviral meningoencephalitis despite being in remission following chemotherapy. DOCK8 deficiency patients are included in the Hyper IgE syndrome spectrum. HSCT poses significant challenges in these children with refractory viral infections. Collaborative work and research are required to decide the optimal care for these children to guide better treatment outcomes.

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Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy

Cited by 6 publications

References 104 publications

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved

Analysis and Regulatory Mechanisms of Platelet-related Genes in Patients with Ischemic Stroke

Emerging spectrum of DOCK8 deficiency in children and challenges associated with providing treatment: experience from a tertiary referral centre in India

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