ライフサイエンスコーパス: PML

1 PML and PML NBs can also regulate mTOR and cell fate dec

2 PML is a component of nuclear domain 10 (ND10) and is in

3 PML is a tumour suppressor and regulator of cell differe

4 PML is frequently downregulated in many cancer types, in

5 PML NBs coordinate chromosomal regions via modification

6 PML nuclear bodies are druggable and could be harnessed

7 PML occurs preferentially in patients with compromised i

8 PML results from JCV reactivation in the setting of impa

9 PML results when oligodendrocytes within immunocompromis

10 PML stabilizes p53 by sequestering MDM2, an E3 ubiquitin

11 PML-like subnuclear bodies, containing XRCC1, juxtaposed

12 PML-RARalpha is recognized to be insufficient for develo

13 s with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations.

14 The cohort comprised 25 PML, 136 natalizumab-treated, and 151 untreated MS patie

15 The t(15;17) translocation generates a PML-RARalpha fusion protein causative for acute promyelo

16 Here, we identify a PML ubiquitination pathway that is mediated by WD repeat

17 uitment of the BTR complex to telomeres in a PML-independent manner bypasses the need for PML in the

18 rtially rescued by two RNF4 SIMs; and (iv) a PML II mutant lacking both lysine SUMOylation and SIM wa

19 aches for treating lung cancer with aberrant PML degradation.

20 t's data are available until 12 months after PML diagnosis.

21 n myeloid cells and its reorganization after PML-RARalpha induction and perform additional analyses i

22 cytic Leukemia/Retinoic Acid Receptor alpha (PML/RARA) driver.

23 e that the PML retinoic acid receptor-alpha (PML-RARalpha) oncofusion protein, which causes acute pro

24 e arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, d

25 Although PML silencing did reduce the sensitivity of U2OS cells t

26 Stat1/2/3 and PML are IFNalpha downstream effectors and are pivotal re

27 etween nuclear aggregate-like assemblies and PML-mediated protein quality control.

28 tion regulates the degradation of PML II and PML II-associated proteins in ND10.

29 our understanding of JC virus infection and PML, and should be taken into account when choosing targ

30 eristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping fe

31 PML and PML NBs can also regulate mTOR and cell fate decisions i

32 HR as a host factor for ZIKV replication and PML protein as a driver of anti-ZIKV intrinsic immunity.

33 We thus conclude that STAT1, SMCHD1, and PML may partly mediate the suppressive effect of IFN-alp

34 nalyses demonstrated that STAT1, SMCHD1, and PML were recruited to cccDNA minichromosomes and phenoco

35 ng SOX3, TNFAIP3, TRAFD1, POU3F3, STAT2, and PML that govern the expression of a large collection of

36 ub-networks regulated by TNFAIP3, TRAFD1 and PML are involved in innate immune response, suggesting t

37 Targeting the interaction of TRIB3 and PML-RARalpha using peptide technology provides a novel t

38 Annual PML risks (per 12 natalizumab infusions) for patients wi

39 suppressant use (n=18 616), estimated annual PML risks per 1000 patients, conditional on having no PM

40 to STAT2, disrupt the formation of antiviral PML-STAT2 NBs, and direct PML degradation.

41 ation of which attenuates the ALT-associated PML bodies (APBs), replication stress and CC formation.

42 zed PML nuclear bodies called ALT-associated PML bodies (APBs).

43 nducible system, we show that ALT-associated PML bodies are disrupted rapidly following DAXX inductio

44 thus artificially engineered ALT-associated PML body (APB)-like condensates in vivo.

45 At PML onset, NfL were 10-fold higher than in the pre-PML c

46 n of inflammation (90% at diagnosis, 100% at PML-IRIS).

47 cifically induce HIRA/PML co-localization at PML nuclear bodies and HIRA recruitment to IFN target ge

48 ction between Topo2a and NSE2 is observed at PML bodies, which are known SUMOylation hotspots.

49 diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the mos

50 o revealed a significant correlation between PML and DDIT4 expression in several cancer types (e.g. l

51 The interplay between PML, Stat1/Stat2, and Stat3 contributes to IFNalpha-medi

52 However, physiological links between PML and oxidative stress response in vivo remain unexplo

53 Through NB biogenesis, PML therefore couples ROS sensing to p53 responses, shed

54 el to investigate their impact on full-blown PML-IRIS latency; (2) an analysis of variance ANOVA to i

55 their prophylactic use to prevent full-blown PML-IRIS seems to negatively impact on the longitudinal

56 n essential component of PML nuclear bodies (PML NBs) frequently lost in cancer.

57 omyelocytic leukemia protein nuclear bodies (PML NBs), an important constituent of nuclear architectu

58 Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that are the hub of n

59 s are promyelocytic leukemia nuclear bodies (PML-NBs), which are subnuclear structures required for t

60 , and ICP0, a viral E3 ligase, degrades both PML and SP100.

61 2 to 21 years with de novo APL confirmed by PML-RARalpha polymerase chain reaction were stratified a

62 We aimed to calculate PML risk estimates from patient-level risk-factor data a

63 DMF appeared generally safe and no carryover PML among investigated cases was observed.

64 In contrast, PML pathogenesis research has been greatly hindered beca

65 e patients in this pooled cohort, cumulative PML risk with or without previous immunosuppressant use

66 ve patients (n=21 696), estimated cumulative PML probability over 6 years (72 infusions of natalizuma

67 high diagnostic certainty for PML ('definite PML' or 'probable PML').

68 T3-ITD APLs, restoring PML/RARA degradation, PML nuclear body reformation, P53 activation, and APL er

69 sequence flanking the RING domain to degrade PML I.

70 in NS5/STAT2/PML NBs that failed to degrade PML, reduce STAT2 expression, or inhibit ISG induction.

71 Here, we used CRISPR/Cas9 to delete PML and APB components from ALT-positive cells to cleanl

72 ed model system for studies of JCV-dependent PML.

73 and B cells in 5 MS patients that developed PML, 4 during natalizumab therapy and one after alemtuzu

74 elapsing-remitting MS patients who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated

75 rapies have a heightened risk for developing PML.

76 Patients subsequently developing PML had similar NfL to other natalizumab-treated MS pati

77 ation of antiviral PML-STAT2 NBs, and direct PML degradation.

78 riptional activity of Aire, while dispersing PML bodies with a viral antagonist restores this activit

79 - and 2-year treated time points, and during PML were analyzed for gene expression by RNA sequencing

80 a significantly higher EDSS increase during PML (0.09 EDSS points per month; p = 0.04) as compared t

81 This study establishes PML as an important regulator of NF-kappaB and demonstra

82 body-negative patients (n=13 996), estimated PML risk was less than 0.07 per 1000 patients (95% CI 0.

83 S5 expression, we found that ZIKV NS5 evicts PML from STAT2 NBs, forming NS5/STAT2 NBs that dramatica

84 However, few PML NB-associated genes have been identified.

85 e criteria for high diagnostic certainty for PML ('definite PML' or 'probable PML').

86 d that (i) the same regulatory mechanism for PML II degradation was detected in cells permissive or n

87 PML-independent manner bypasses the need for PML in the ALT pathway, suggesting that BTR localization

88 This suggested an essential role for PML in IFNalpha's anti-angiogenic function.

89 elopment of novel therapeutic strategies for PML.

90 pectively) despite a very high suspicion for PML based on lesion evolution and signs of PML-immune re

91 setting in which MRI is frequently used for PML screening.

92 apsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovi

93 Upregulated Mad1 displaces MDM2 from PML, freeing it to ubiquitinate p53.

94 Furthermore, PML promotes turnover of nuclear Stat3, and knockdown of

95 of 37 249 patients in the pooled cohort had PML.

96 l interferons (IFN) specifically induce HIRA/PML co-localization at PML nuclear bodies and HIRA recru

97 clerosis - have led to a surge of iatrogenic PML.

98 Here, we identify PML as a reactive oxygen species (ROS) sensor.

99 717 genes implicated in cancer, identifying PML-RARA fusions in the NB4 cell line in <15 h sequencin

100 and specificity assessments for identifying PML cases in an index cohort.

101 stem by knocking down USP18 altered IFNalpha-PML axis-mediated inhibition of endothelial cell migrati

102 many become SUMO-modified and accumulate in PML bodies.

103 will help unravel the role of astrocytes in PML pathogenesis.IMPORTANCE Animal models are crucial in

104 s significantly less affected by IFN-beta in PML(-/-) cells than in parental PML(+/+) cells, and (iii

105 iii) viral yields are significantly lower in PML(-/-) cells exposed to low ratios of virus per cell c

106 vement of different regulatory mechanisms in PML II recognition by ICP0 in HSV-1 infection.

107 ells than in parental SP100(+/+) cells or in PML(-/-) cells.

108 ften hijack the cellular factors resident in PML-NBs to promote their proliferation in host cells.

109 Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathologi

110 They also contain other factors, including PML, poly(ADP-ribose) polymerase 1 (PARP1), ligase IIIal

111 ne syndrome type-1, form foci with increased PML body association.

112 al ATRA response is unaffected, ATRA-induced PML/RARA degradation is blunted, as is PML nuclear body

113 comprehensive understanding of JCPyV-induced PML pathogenesis is needed to define determinants that p

114 of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflamma

115 ear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered tr

116 Here, we investigated PML's role in the regulation of Stat1/2/3 activity.

117 duced PML/RARA degradation is blunted, as is PML nuclear body reformation and activation of P53 signa

118 rus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a majo

119 S neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

120 pathology and may provide insight into JCPyV-PML pathogenesis.

121 are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape fr

122 above 150 m depth in the polar mixed layer (PML) and halocline.

123 Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, bu

124 uding ALT-associated promyelocytic leukemia (PML) bodies (APBs), telomere sister chromatid exchanges

125 ustered telomeres in promyelocytic leukemia (PML) bodies, represented as large bright telomere foci.

126 Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structu

127 Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in

128 rentially recognizes promyelocytic leukemia (PML) isoforms.

129 , with disruption of promyelocytic leukemia (PML) nuclear bodies (NBs) mediated by the PML-retinoic a

130 Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, incl

131 ed Mad1 localizes to ProMyelocytic Leukemia (PML) nuclear bodies in breast cancer and cultured cells.

132 by associating with promyelocytic leukemia (PML) nuclear bodies, ensuring its availability upon mito

133 containing canonical promyelocytic leukemia (PML) nuclear body protein SP100 concentrated in a periph

134 formed by STAT2 and promyelocytic leukemia (PML) protein are present constitutively and enhance inna

135 ining 1 (SMCHD1), or promyelocytic leukemia (PML) protein increased basal level of cccDNA transcripti

136 The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bo

137 the accumulation of promyelocytic leukemia (PML) protein, BRCA1 and the SMC5/6 complex at telomeres,

138 munity driven by the promyelocytic leukemia (PML) protein, which limits ZIKV replication.

139 r suppressor protein promyelocytic leukemia (PML).

140 progressive multifocal leukoencephalopathy (PML) and full-blown immune reconstitution inflammatory s

141 progressive multifocal leukoencephalopathy (PML) during natalizumab treatment.

142 progressive multifocal leukoencephalopathy (PML) in individuals with depressed immune status.

143 progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with na

144 progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis receiving natal

145 Progressive multifocal leukoencephalopathy (PML) is a devastating CNS infection caused by JC virus (

146 Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by reactivation of JC pol

147 Progressive multifocal leukoencephalopathy (PML) is a rare, potentially devastating myelin-degrading

148 Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the cent

149 Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused

150 progressive multifocal leukoencephalopathy (PML) is caused by the infection of particular brain cell

151 progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease.

152 progressive multifocal leukoencephalopathy (PML), a rare, fatal, demyelinating disease.

153 progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in indivi

154 progressive multifocal leukoencephalopathy (PML), and the occurrence of rebounds or disease activity

155 progressive multifocal leukoencephalopathy (PML).

156 progressive multifocal leukoencephalopathy (PML).

157 is computed from posterior mean liabilities (PML) under a liability threshold model; however, LT-Fam

158 ls to metabolic stress induced by metformin, PML loss did not inhibit the upregulation of DDIT4 in re

159 ses in patient-derived APL cells with native PML-RARalpha.

160 per 1000 patients, conditional on having no PML before that year, ranged from 0.01 (0.00-0.03) in ye

161 oped PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr) were included in the

162 Moreover, arsenic targeting of normal PML also contributes to APL response in vivo.

163 e still classified as 'possible PML' or 'not PML' (6 (21.5%) and 2 (7.1%) patients, respectively) des

164 Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflamm

165 Patients from the Dutch-Belgian NTZ-PML cohort (n=28) were reviewed at the time of first dia

166 imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating an

167 ation on brain MRI scans of inflammatory NTZ-PML patients.

168 gressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of infla

169 PML has low sensitivity for diagnosis of NTZ-PML in a real-world clinical setting in which MRI is fre

170 2, this complex fails to localize to nuclear PML bodies.

171 The amounts of PML and SP100 and the number of ND10 structures increase

172 The association of PML-NB proteins and HBV is being addressed in a number o

173 a (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer.

174 The current case definition of PML has low sensitivity for diagnosis of NTZ-PML in a re

175 SIM interaction regulates the degradation of PML II and PML II-associated proteins in ND10.

176 (SIM(362-364)) to trigger the degradation of PML isoforms II, IV, and VI, while using a bipartite seq

177 biomarker associated with the development of PML in MS patients treated with NTZ.

178 s achieved in part through the disruption of PML-NBs and the inhibition of robust ISG transcription.I

179 ML, and may complicate a valid estimation of PML incidence during NTZ therapy.

180 ty of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25.

181 STAT3 on Ser727, and increased expression of PML, a STAT3 transcriptional target.

182 gh degradation or functional inactivation of PML NB proteins, which are recruited to viral genomes in

183 The increasing incidence of PML in patients receiving immunotherapeutic and chemothe

184 Thus, (i) the interaction of PML with viral components facilitates the initiation of

185 turnover of nuclear Stat3, and knockdown of PML mitigates the effect of LLL12, a selective Stat3 inh

186 elay diagnosis and appropriate management of PML, and may complicate a valid estimation of PML incide

187 represent an early and accessible marker of PML.

188 response were not detected at the moment of PML onset.

189 Conversely, normal numbers of PML NBs were restored upon transition to latency or by d

190 ics were followed up until the occurrence of PML-IRIS.

191 apeutic approaches calls for reassessment of PML pathophysiology and clinical course.

192 agnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRI

193 Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML

194 individualised annual prediction of risk of PML in patients receiving natalizumab for multiple scler

195 emitting multiple sclerosis, at high risk of PML, were switched from NTZ to DMF and underwent neurolo

196 study thus reveals a new regulatory role of PML bodies in Aire function, and highlights the interpla

197 tant patients, demonstrating the key role of PML in APL cure.

198 1 and Stat3, indicating an important role of PML in regulating Stat1 and Stat3 activity.

199 sponses, shedding a new light on the role of PML in senescence or stem cell biology.

200 A-based regimens, and stress the key role of PML nuclear bodies in APL eradication by the ATRA/arseni

201 molecular mechanisms underlying the role of PML-RARalpha in leukemogenesis remain largely unknown.

202 novel topological insights for the roles of PML-RARalpha in transforming myeloid cells into leukemia

203 r PML based on lesion evolution and signs of PML-immune reconstitution inflammatory syndrome on MRI,

204 Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-re

205 had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in t

206 Studies of PML, however, have been hampered by the lack of an immor

207 impaired in 4 out 5 patients at the time of PML development; ii) T-cell repertoire was restricted; i

208 Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but diff

209 -cell expansions were mounted at the time of PML.

210 ne checkpoint inhibitors in the treatment of PML is warranted.

211 rategies for intercepting the progression of PMLs to lung cancer.

212 identification of four molecular subtypes of PMLs with distinct differences in epithelial and immune

213 gulating the expression of STAT1, SMCHD1, or PML significantly increased the level of viral RNAs with

214 ast, ectopic expression of STAT1, SMCHD1, or PML significantly reduced cccDNA transcription activity.

215 Thus, similar to p53, PML exerts basal antioxidant properties but also drives

216 IFN-beta in PML(-/-) cells than in parental PML(+/+) cells, and (iii) viral yields are significantly

217 ios of virus per cell compared with parental PML(+/+) cells.

218 patients were still classified as 'possible PML' or 'not PML' (6 (21.5%) and 2 (7.1%) patients, resp

219 ssed genes in the RNA sequencing between pre-PML and NTZ-ctr patients, pathway analysis revealed a hi

220 lloproteinase 9 (MMP9) was validated; in pre-PML patients, MMP9 protein levels were significantly red

221 eening cohort and a validation cohort of pre-PML and NTZ-ctr patients.

222 set, NfL were 10-fold higher than in the pre-PML condition and in natalizumab-treated or untreated MS

223 nts who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr) were inc

224 rtainty for PML ('definite PML' or 'probable PML').

225 ature identifies subjects with Proliferative PMLs from normal-appearing uninvolved large airway brush

226 haracterized by the oncogenic fusion protein PML-RARalpha, a major etiological agent in APL.

227 it upregulates the tumor suppressor protein PML.

228 BC9, and the promyelocytic leukemia protein (PML) and thus was not due to nonspecific SUMO conjugatio

229 raction with promyelocytic leukemia protein (PML) bodies, sites of many nuclear processes including p

230 stant [e.g., promyelocytic leukemia protein (PML), SP100, death domain-associated protein (Daxx)] and

231 uid sample of a 73-year-old woman with rapid PML onset, 3 distinct JCPyV populations could be identif

232 1-contaning foci constitute newly recognized PML-like nuclear bodies that accrete and locally deliver

233 rming NS5/STAT2 NBs that dramatically reduce PML expression in hBMECs and inhibit the transcription o

234 ICP0 E3 ubiquitin ligase activity regarding PML II degradation.

235 harmacologic inhibition as tools to regulate PML stability and impair latency establishment.

236 as an oncoprotein that negatively regulates PML via ubiquitination to promote lung cancer progressio

237 apies greatly reduce the risk of HIV-related PML, but many modern treatments for cancers, organ trans

238 apeutic response in FLT3-ITD APLs, restoring PML/RARA degradation, PML nuclear body reformation, P53

239 zed, in part, by the presence of specialized PML nuclear bodies called ALT-associated PML bodies (APB

240 MO site mutant (K252R) resulted in NS5/STAT2/PML NBs that failed to degrade PML, reduce STAT2 express

241 inical need to define biomarkers to stratify PML risk and develop anti-JCPyV interventions.

242 he lack of a tractable animal model to study PML pathogenesis.

243 As such, PML-NBs serve as an important hurdle for viruses to over

244 Many people who survive PML are left with neurological sequelae and some with pe

245 As the number of people who survive PML increases, this lack of viral clearance could create

246 immune reconstitution inflammatory syndrome (PML-IRIS).

247 immune reconstitution inflammatory syndrome (PML-IRIS).

248 d that PML NBs are hyper-SUMOylated and that PML protein is degraded via the ubiquitin-proteasome pat

249 We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal

250 We demonstrate that PML promotes TNFalpha-induced transcriptional responses

251 mary endothelial cells, we demonstrated that PML positively regulates Stat1 and Stat2 isgylation, a u

252 We also demonstrated that PML shared a large cohort of regulatory genes with Stat1

253 regulator of NF-kappaB and demonstrates that PML-RARalpha dysregulates NF-kappaB.

254 We discover that PML-RARalpha mediates extensive chromatin interactions g

255 Emerging evidence that PML can be ameliorated with novel immunotherapeutic appr

256 We found that PML is required for the ALT mechanism, and that this nec

257 We found that PML NBs are hyper-SUMOylated and that PML protein is deg

258 ute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis.

259 DNA and RNA immuno-FISH reveal that PML NBs are closely associated with actively transcribed

260 Earlier studies have shown that PML has three key functions.

261 tion at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of i

262 a (PML) nuclear bodies (NBs) mediated by the PML-retinoic acid receptor alpha (RARalpha) oncoprotein.

263 be essential for the exit of Sp110 from the PML-NB during HBV infection and HBx recruitment on the p

264 goes a deSUMOylation-driven release from the PML-NB in the presence of HBV.

265 evade host immune response by hijacking the PML-NB protein Sp110, and therefore, we propose it to be

266 pg/L) of measured PFOA concentrations in the PML (mean 32 +/- 15 pg/L).

267 overed the importance of multivalency in the PML II-ICP0 interaction network and report the involveme

268 DAXX's localization in the PML nuclear bodies also plays roles in transcriptional r

269 l known that certain other components of the PML NB complex play an important role during an intrinsi

270 We also demonstrate that the PML retinoic acid receptor-alpha (PML-RARalpha) oncofusi

271 Here, we report that the PML-NB protein Speckled 110 kDa (Sp110) is SUMO1-modifie

272 stic work-up and during follow-up, using the PML diagnostic criteria as proposed in a consensus state

273 ema (10%) at diagnosis, as compared with the PML-IRIS stage (40%).

274 Clinically, this PML degradation pathway is hyperactivated in lung cancer

275 Directing Aire to PML bodies impairs the transcriptional activity of Aire,

276 interacting motif) condensates, analogous to PML bodies, and thus artificially engineered ALT-associa

277 Treatment with PLEX was not associated to PML-IRIS latency (hazard ratio [HR] = 1.05; p = 0.92), b

278 In contrast to PML(-/-) cells, SP100(-/-) cells retain the sensitivity

279 nd restores the localization of ATRX/DAXX to PML bodies.

280 tly bound to chromatin and were localized to PML nuclear bodies.

281 with naked plasmid DNA, HIRA re-localizes to PML bodies, sites of cellular anti-viral activity.

282 ine determinants that predispose patients to PML, a goal whose urgency is heightened by the lack of a

283 ome, and we lack tools to identify and treat PMLs at risk for progression to cancer.

284 TNFalpha-treated PML(-/-) cells show normal IkappaBalpha degradation and

285 enetically engineered mouse models, the WDR4/PML axis elevates intratumoral Tregs and M2-like macroph

286 The WDR4/PML axis induces a set of cell-surface or secreted facto

287 Pml(-/-) cells accumulate ROS, whereas PML expression decreases ROS levels.

288 It remains to be established whether PML pathogenesis is driven by one or several neurotropic

289 findings uncover a novel mechanism by which PML loss may contribute to mTOR activation and cancer pr

290 ucidated an unappreciated mechanism in which PML, an IFNalpha-inducible effector, possess potent angi

291 ight every 4 to 6 weeks to eight adults with PML, each with a different underlying predisposing condi

292 e C-terminus of Mad1 directly interacts with PML, and this interaction is enhanced by sumoylation.

293 One patient with PML had a single neurotropic strain with rearranged NCCR

294 ti-JC virus immune activity in patients with PML was unknown.

295 adiological data of 42 Italian patients with PML were analyzed.

296 neurotropic JCPyV strains of 3 patients with PML without the bias caused by assembly of short sequenc

297 th the hypothesis that in some patients with PML, pembrolizumab reduces JC viral load and increases C

298 in the cerebrospinal fluid of patients with PML.

299 ues, separately for patients with or without PML.

300 natalizumab infusions) for patients without PML in the preceding year were estimated using condition