Analysis of p53, K‐ras, c‐kit, and β‐catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China

Hoshida, Yoshihiko; Hongyo, Tadashi; Jia, Xinshan; He, Yong; Hasui, Kazuhisa; Zhang, Dong; Luo, Wen; Ham, Maria Francisca; Nomura, Taisei; Aozasa, Katsuyuki

doi:10.1111/j.1349-7006.2003.tb01436.x

Cited by 45 publications

(42 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, KIT mutations are not specific for mastocytosis. 1,[15][16][17] KIT is a known oncogene and gain-of-function mutations have been identified in systemic mastocytosis, by far the most common (480%) being found in exon 17 where a somatic point mutation, A4T in nucleotide 2468 of KIT cDNA, results in the replacement of an aspartic acid by valine at codon 816 (D816V). 18 This mutation leads to a ligandindependent constitutive activation and autophosphorylation of KIT.…”

Section: Discussionmentioning

confidence: 99%

Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

et al. 2009

View full text Add to dashboard Cite

In the World Health Organization classification, one major and four minor criteria are specified for the diagnosis of systemic mastocytosis. We report our experience using these criteria to diagnose systemic mastocytosis involving bone marrow. A total of 59 patients with clinically suspected systemic mastocytosis underwent comprehensive bone marrow examination, including immunophenotyping by immunohistochemistry and/or flow cytometry and molecular studies for KIT exon 17 mutations. Serum tryptase levels were also assessed. Of these 59, 53 (90%) patients met the diagnostic criteria for systemic mastocytosis. In these patients, multifocal dense infiltrates of mast cells, the major criterion, was observed in 36 (68%) patients. Atypical mast cell morphology was observed in 53 (100%), an aberrant immunophenotype was identified in 50 of 52 (96%), KIT mutation was present in 33 of 44 (75%), and an elevated serum tryptase (420 ng/ml) was detected in 44 of 52 (85%). In the six patients in which bone marrow examination could not confirm systemic mastocytosis, one had systemic mastocytosis involving spleen, one patient had chronic idiopathic myelofibrosis, and four had no specific diagnosis, but systemic mastocytosis was still considered most likely. Of these six patients, atypical mast cell morphology was identified in five, aberrant immunophenotype in five, KIT mutation in two, and elevated serum tryptase in two. None of these cases met the major criteria. We conclude that the World Health Organization criteria are useful for the diagnosis of systemic mastocytosis in bone marrow specimens. The results also show the relative values of traditional morphologic criteria (ie, major criterion) and the results of ancillary testing (ie, minor criteria). However, as illustrated by the case of splenic systemic mastocytosis as well as the patient with chronic idiopathic myelofibrosis, the current World Health Organization system is neither completely sensitive nor specific for systemic mastocytosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The subsequent accumulation of ␤-catenin leads to its nuclear translocation and transcriptional activity (47). Interestingly, mutations of ␤-catenin are frequently associated with NK and T cell lymphoproliferative disorders (49,50) suggesting that ␤-catenin defects may also contribute to a loss of lymphocyte homeostasis. Our results showed that in normal NK cells, 2B4 stimulation resulted in cytoplasmic and nuclear accumulation of ␤-catenin implying that in NK cells, as in B cells, GSK-3 phosphorylation results in ␤-catenin dephosphorylation, dissociation from GSK-3, and nuclear translocation of ␤-catenin.…”

Section: Discussionmentioning

confidence: 99%

Role for Glycogen Synthase Kinase-3 in NK Cell Cytotoxicity and X-Linked Lymphoproliferative Disease

Aoukaty

Tan

2005

The Journal of Immunology

View full text Add to dashboard Cite

NK cells from individuals with X-linked lymphoproliferative (XLP) disease exhibit functional defects when stimulated through the NK receptor, 2B4 (CD244). These defects are likely a consequence of aberrant intracellular signaling initiated by mutations of the adaptor molecule SLAM-associated protein. In this report, we show that NK cells from individuals with XLP but not healthy individuals fail to phosphorylate and thereby inactivate glycogen synthase kinase-3 (GSK-3) following 2B4 stimulation. Lack of GSK-3 phosphorylation prevented the accumulation of the transcriptional coactivator β-catenin in the cytoplasm and its subsequent translocation to the nucleus. Potential signaling pathways leading from 2B4 stimulation to GSK-3 phosphorylation were also investigated. Ligation of 2B4 resulted in the phosphorylation of the guanine nucleotide exchange factor, Vav-1, and subsequent activation of the GTP-binding protein Rac-1 (but not Ras) and the serine-threonine kinase Raf-1 in healthy but not XLP-derived NK cells. In addition, the activity of MEK-2 (but not MEK-1) was up-regulated, and Erk1/2 was phosphorylated in normal NK cells but not those from an individual with XLP suggesting that these proteins relay SLAM-associated protein-dependent signals from 2B4. Finally, inactivation of GSK-3 using a specific inhibitor of GSK-3β increased the cytotoxicity and cytokine secretion of both healthy and XLP NK cells. These data indicate that the signaling of 2B4 in NK cells is mediated by GSK-3 and β-catenin, possibly through a signal transduction pathway that involves Vav-1, Rac-1, Raf-1, MEK-2, and Erk1/2 and that this pathway is aberrant in individuals with XLP.

show abstract

“…Mutations of p53 have been demonstrated, with variable frequencies (24 to 60%). Mutation of c-kit can also be frequently demonstrated, as far as Fas gene mutations (Hoshida et al, 2003;Shen et al, 2002). The most common cytogenetic aberration is deletion of 6q.…”

Section: Extranodal Nk/t Cell Lymphoma Nasal Typementioning

confidence: 99%

Physiological and Pathological Aspects of Human NK Cells

Vitale¹,

Zambello²,

Balsamo³

et al. 2012

Hematology - Science and Practice

View full text Add to dashboard Cite

Analysis of p53, K‐ras, c‐kit, and β‐catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China

Cited by 45 publications

References 17 publications

Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

Role for Glycogen Synthase Kinase-3 in NK Cell Cytotoxicity and X-Linked Lymphoproliferative Disease

Physiological and Pathological Aspects of Human NK Cells

Contact Info

Product

Resources

About