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Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1.
this study shows that mutation in IKAROS results in B cell hyper-responsiveness and autoimmunity
Deletions of at least 1 IKZF1 exon were observed in 7/34 PRE-B-ALL patients: 3 with 1 exon deleted; 1 with 2 exons, 1 with 5 exons, 1 with 6 exons, and 1 patient with a complete IKZF1 deletion. The frequency of the IKZF1 gene deletion in a Mexican pediatric population with preB ALL was 20.6%.
IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1(plus).
acute lymphoblastic leukemia children with IKZF1 deletion have worse early treatment response
we report on the first truncating IKZF1 mutation associated with IKAROS haploinsufficiency and illustrate an unexpectedly late and variable block in central and peripheral B-cell development in 2 patients and their asymptomatic mother.
Review: a concise overview on the role of IKZF1 during normal lymphopoiesis and the pathways that contribute to leukemia pathogenesis as a consequence of altered IKZF1 function.
Quantitative detection of IKZF1 deletion by digital PCR in patients with acute lymphoblastic leukemia.
Study has shown that BCAT1 and IKZF1 methylation are common events in colorectal cancer (CRC) with almost all cancer tissues showing significant levels of methylation in the two genes. The presence of ctDNA in blood is stage-related and show rapid reversion to negative following surgical resection. Monitoring methylated BCAT1 and IKZF1 levels could therefore inform adequacy of surgical resection.
It was found that the variants rs10740055 of ARID5B and rs6964823 of IKZF1 act individually and additively as risk factors in the development of leukemia in the populations of Northern India. The variants rs6964823 (IKZF1) and rs10740055 (ARID5B) showed significant associations with odds ratio (OR) and p-values of 1.5 (1.0-2.3 at 95% confidence interval [CI]) and 0.04; and 2.5 (1.5-4.1 at 95% CI) and 0.0002, respectively
Single nucleotide polymorphism association analysis showed that the Toll-like receptor 3 (TLR3), prostaglandin-E receptor 3 (PTGER3), and IKZF1 gene were significantly associated with cold medicine-Stevens-Johnson syndrome and toxic epidermal necrolysis with severe ocular complications.
functional Ikaros negatively correlated with FUT4 expression
Study identified a coding germline IKZF1 variation as a risk factor for genetic predisposition to acute lymphoblastic leukemia (ALL) and showed that the majority of variants have deleterious effects on IKAROS protein functions. Moreover, these IKZF1 variants demonstrate differences in the type and magnitude of their effects.
Combination of IKAROS family zinc finger 1 protein (IKZF1) deletion and minimal residual disease (MRD) status enable better risk stratification of patients for assignment to optimal therapeutic strategies.
The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1.
heterozygous mutation decreases plasmacytoid dendritic cell numbers and expands conventional dendritic cells
IKZF1 has a role in childhood B-cell precursor acute lymphoblastic leukemia
this study shows that alteration in Ikaros expression promotes B-1 cell differentiation into phagocytes
Our results demonstrate that the IKAROS promotes PHF2 expression, and suggest that PHF2 (low) expression works with the IKAROS gene deletion to drive oncogenesis of ALL
these data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge
IKZF1 is upregulated in granulocytes, B cells, CD4- and CD8- T cells, and natural killer (NK) cells; it is downregulated in erythroblasts, megakaryocytes, and monocytes.
The results introduce Rgag4 to the repertoire of effectors serving to couple the chromatin remodeler Ikaros with the hormonal stress response.
Study results identify Ikaros as a key player in the early steps of dendritic cells development.
we identified IKZF1 as a novel regulator of glucocorticoid -induced transcriptional responses and a critical determinant of glucocorticoid -mediated cell death in normal and leukemic B cells
These data describe a novel regulatory mechanism through which STAT3 and the Ikaros zinc finger transcription factors Aiolos and Ikaros cooperate to regulate Bcl-6 expression.
Ikaros is a transcriptional regulator required for maintaining levels of Foxo1 gene expression in naive T-cells.
ADAMTS10 is identified as a potential functional integrator of the Ikaros-CtBP chromatin remodeling network.
this study shows that ablation of Ikzf1 in RORgammat+ group 3 innate lymphoid cells results in increased expansion and cytokine production, and protection against infection and colitis
Sumoylated Ikaros is less effective than unsumoylated forms at inhibiting the expansion of murine leukemic cells, and Ikaros sumoylation is abundant in human B-cell acute lymphoblastic leukemic cells, but not in healthy peripheral blood leukocytes. Our results suggest that sumoylation may be important in modulating the tumor suppressor function of Ikaros
our results identify BTG1 as a tumor suppressor in leukemia that, when deleted, strongly enhances the risk of relapse in IKZF1-deleted B-cell precursor acute lymphoblastic leukemia, and augments the glucocorticoid resistance phenotype mediated by the loss of IKZF1 function.
These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.
These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.
Ikaros functions as a guardian of B-1 lymphoid pattern, and that its absence directs the differentiation of B-1 cells into phagocytes.
Ikaros is a fundamental regulator of PRC2 function in developing T cells.
Ikaros/Ets1 binding has a role on Ikzf1 expression that is exerted at least through its promoter
deletions on chromosomes 4 and 11 affecting Cdkn2a and Ikaros are a prominent feature of young adult irradiation-induced T-cell lymphoma.. tumors arising after irradiation suffer a second hit in Pten by mis-segregation or recombination
Murine pancreatic adenocarcinoma reduces Ikaros expression and disrupts T cell homeostasis
The Ikaros family of DNA-binding proteins are critical regulators of lymphocyte differentiation. (Review)
mice with targeted deletion of the fourth DNA-binding zinc finger of the transcription factor Ikaros had increased IL-22-producing, but not IL-17-producing, CD4(+) T cells in the gut.
This gene encodes a transcription factor that belongs to the family of zinc-finger DNA binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. All isoforms share a common C-terminal domain, which contains two zinc finger motifs that are required for hetero- or homodimerization, and for interactions with other proteins. The isoforms, however, differ in the number of N-terminal zinc finger motifs that bind DNA and contain the nuclear localization signal, resulting in members with and without DNA-binding properties. Only few isoforms contain the requisite three or more N-terminal zinc motifs that confer high affinity binding to a specific core DNA sequence element in the promoters of target genes. The non-DNA-binding isoforms are largely found in the cytoplasm, and thought to function as dominant negative factors. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL).
CLL-associated antigen KW-6
, DNA-binding protein Ikaros
, Ikaros (zinc finger protein)
, ikaros family zinc finger protein 1
, lymphoid transcription factor LyF-1
, zinc finger protein, subfamily 1A, 1 (Ikaros)
, Ikaros transcription factor
, KAROS family zinc finger 1 (Ikaros)
, IKAROS family zinc finger 1 (Ikaros)
, DNA-binding protein Ikaros-like
, zinc finger protein subfamily 1A, 1