PD-1 Regulates the Growth of Human Mastocytosis Cells

Kataoka, Tatsuki R.; Fujimoto, Masakazu; Moriyoshi, Koki; Koyanagi, Itsuko; Ueshima, Chiyuki; Kono, Fumihiko; Tsuruyama, Tatsuaki; Okayama, Yoshimichi; Ra, Chisei; Haga, Hironori

doi:10.2332/allergolint.12-oa-0450

Cited by 23 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…They incubated with primary antibodies against CD25 (clone 4C9, dilution 1:1; Nichirei Bioscience) and CD45RO (clone UCLH-1, dilution 1:100; DAKO). 13,14 The bound antibodies were detected using the Histofine Simple Stain MAX PO reagent with diaminobenzidine as a chromogen, and the sections were counterstained with Mayer's hematoxylin. IHC analysis with anti-CD3 (clone 2GV6, dilution 1:1; Roche) and anti-CD4 (clone SP35, dilution 1:1; Roche) antibodies was performed with the Ventana Benchmark automated staining system (Ventana Medical Systems) according to the manufacturer's instruction.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Nagata

Kontani

Enami

et al. 2016

Blood

Self Cite

103

View full text Add to dashboard Cite

Key Points• RHOA mutations are common in ATLL and show a unique distribution compared with other T-cell lymphomas.• Depending on patients, functionally distinct RHOA mutations are clonally selected and involved in the pathogenesis of ATLL.Adult T-cell leukemia/lymphoma (ATLL) is a distinct form of peripheral T-cell lymphoma with poor prognosis, which is caused by the human T-lymphotropic virus type 1 (HTLV-1). In contrast to the unequivocal importance of HTLV-1 infection in the pathogenesis of ATLL, the role of acquired mutations in HTLV-1 infected T cells has not been fully elucidated, with a handful of genes known to be recurrently mutated. In this study, we identified unique RHOA mutations in ATLL through whole genome sequencing of an index case, followed by deep sequencing of 203 ATLL samples. RHOA mutations showed distinct distribution and function from those found in other cancers. Involving 15% (30/203) of ATLL cases, RHOA mutations were widely distributed across the entire coding sequence but almost invariably located at the guanosine triphosphate (GTP)-binding pocket, with Cys16Arg being most frequently observed. Unexpectedly, depending on mutation types and positions, these RHOA mutants showed different or even opposite functional consequences in terms of GTP/guanosine diphosphate (GDP)-binding kinetics, regulation of actin fibers, and transcriptional activation. The Gly17Val mutant did not bind GTP/GDP and act as a dominant negative molecule, whereas other mutants (Cys16Arg and Ala161Pro) showed fast GTP/GDP cycling with enhanced transcriptional activation. These findings suggest that both loss-and gain-of-RHOA functions could be involved in ATLL leukemogenesis. In summary, our study not only provides a novel insight into the molecular pathogenesis of ATLL but also highlights a unique role of variegation of heterologous RHOA mutations in human cancers. (Blood. 2016;127(5):596-604)

show abstract

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Nagata

Kontani

Enami

et al. 2016

Blood

Self Cite

103

View full text Add to dashboard Cite

show abstract

“…17 In 2013, Kataoka and colleagues published the first report of PD-1 expression in CM, confirmed with reverse transcription-polymerase chain reaction, western blotting, and flow cytometry. They documented that 10 of 30 cases of CM expressed PD-1.…”

Section: Discussionmentioning

confidence: 99%

“…They documented that 10 of 30 cases of CM expressed PD-1. 17 The patients with CM were not subclassified as to type, but the widespread ages that are given suggest a mix of CM and SM patients, where the latter had likely MIS lesions. Thus, we cannot easily separate whether the CM patients that expressed PD-1 were in fact only CM patients.…”

Section: Discussionmentioning

confidence: 99%

Variability of PD-L1 expression in mastocytosis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Cytological specimens were fixed in 100% methanol, and pathological specimens were fixed in formalin and paraffin-embedded. Both types of specimen were stained, as described in a previous report [16], in addition to ALK immunohistochemical staining of pathological specimens, which was performed using the intercalated antibody-enhanced polymer (iAEP) method [17]. …”

Section: Methodsmentioning

confidence: 99%

An inflammatory myofibroblastic tumor exhibiting immunoreactivity to KIT: a case report focusing on a diagnostic pitfall

et al. 2014

Self Cite

View full text Add to dashboard Cite

Inflammatory myofibroblastic tumors (IMTs) and gastrointestinal stromal tumors (GISTs) are both spindle cell tumors, and occur rarely in the wall of the urinary bladder. In general, immunostaining allows differentiation of IMTs and GISTs. Most IMTs are positive for anaplastic lymphoma kinase (ALK) and negative for KIT, whereas most GISTs are ALK-negative and KIT-positive. Here, we describe a case of a spindle cell tumor in the wall of the urinary bladder. The spindle cells were positive for both ALK and KIT, and it was thus difficult to determine whether the tumor was an IMT or a GIST. We eventually diagnosed an IMT, because ALK gene rearrangement was confirmed by fluorescent in-situ hybridization. Cytoplasmic staining for KIT and the absence of other GIST markers, including DOG1 and platelet-derived growth factor α, indicated that the tumor was not a GIST. Therefore, IMTs should be included in the differential diagnosis of spindle cell tumors, even those that are KIT-positive.

show abstract

PD-1 Regulates the Growth of Human Mastocytosis Cells

Abstract: PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.

Cited by 23 publications

References 25 publications

Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Variability of PD-L1 expression in mastocytosis

An inflammatory myofibroblastic tumor exhibiting immunoreactivity to KIT: a case report focusing on a diagnostic pitfall

Contact Info

Product

Resources

About