ライフサイエンスコーパス: JAK2

1 ythemia (ET) with nonmutated Janus kinase 2 (JAK2).

2 y, which places CRY activity downstream from JAK2.

3 or STAT3 via gp130 and its downstream kinase JAK2.

4 c expression, and this effect is mediated by JAK2.

5 , we questioned whether TFEB is regulated by JAK2.

6 s, whereas progenitors are less dependent on Jak2.

7 mutations lead to constitutive activation of JAK2.

8 ibitors that bind the active conformation of JAK2.

9 xpression in RAW 264.7 cells did not require JAK2.

10 V617F carriers, we replicated the germ line JAK2 46/1 haplotype (rs59384377: odds ratio [OR] = 2.4,

11 tudies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and

12 itinib, which preferentially blocks JAK1 and JAK2, abolished the proliferation of cells transformed b

13 n regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are large

14 AK2/STAT5 signaling, is necessary to augment JAK2 activity caused by E846D above a threshold level le

15 B treatment nor myeloid-specific deletion of JAK2 affected FPN1 expression.

16 ued by expression of a constitutively active Jak2 allele.

17 At two loci (JAK2 and A1CF), experimental analysis in mice showed lip

18 In a humanized BC CML mouse model, combined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal c

19 Pacritinib, which inhibits both JAK2 and FLT3, induced spleen responses with limited mye

20 or homologous Leu(857) mutations of JAK1 and JAK2 and for JAK3(L875H).

21 f less than 20 nM, is <100 nM potent against JAK2 and HDAC11, and is selective for the JAK family aga

22 A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM po

23 required for T cell differentiation, such as JAK2 and IL12RB2, are regulated by H3K27me3.

24 JAK2 and MPL mutant cell lines were sensitive to CHZ868,

25 next-generation sequencing (NGS) targeted on JAK2 and MPL.

26 expressed EGFR significantly correlated with JAK2 and PD-L1 expression in a large cohort of HNC speci

27 formed cells, no synergy is observed between JAK2 and PI3-K inhibitors in inhibiting cytokine-indepen

28 This occurs independently from JAK2 and Rac signalling, but is required for full phosph

29 impaired by Gab2 deletion via regulation of Jak2 and signal transducer and activator of transcriptio

30 is good evidence for activation of the JAK1/JAK2 and signal transducer and activator of transcriptio

31 Moreover, an increase in phosphorylated JAK2 and STAT3 accompanied chemical induction of LTD and

32 the IL-23 signaling pathway, such as IL-23R, JAK2 and STAT3, have been characterized, but elements un

33 injections reveal a significant reduction in JAK2 and STAT5 phosphorylation in liver, but not in skel

34 BL fusion protein, the V617F substitution in JAK2 and the V600K substitution in BRAF.

35 s, they differentially use the Janus kinase (Jak2) and phosphatidylinositol 3-kinase (Pi3k) signaling

36 crease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activ

37 phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and EPOR that activate JAK/STAT signaling.

38 -DLBCL, which shows higher levels of IL10RA, JAK2, and STAT3 but lower levels of BCL6 than GC-DLBCL a

39 ctor receptor (EGFR) utilize Janus kinase 2 (JAK2) as a common signaling node to transmit tumor cell-

40 mide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary

41 Our findings show that mutated FLT3-ITD and JAK2 augment ROS production and HR, shifting the cellula

42 nd Box2 motifs in IL-12Rbeta1 and an unusual Jak2-binding site in IL-23R by the use of deletion and s

43 (Tyk) 2 associates with IL-12Rbeta1, whereas Jak2 binds to IL-23R and also to IL-12Rbeta2.

44 munoprecipitation of Tyk2 by IL-12Rbeta1 and Jak2 by IL23R supported these findings.

45 ic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria

46 s, which are largely defined by mutations in JAK2, CALR, or MPL In the B-cell lymphomas, detection of

47 egakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic crit

48 in and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation.

49 a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is

50 The identification of somatic mutations of JAK2, CALR, or MPL, found in about 90% of patients, has

51 tricted driver mutations, including those in JAK2, calreticulin (CALR), and myeloproliferative leukem

52 Importantly, the kinase activity of PAX5-JAK2 can be efficiently blocked by JAK2 inhibitors, rend

53 hatase SHP2 and prolonged phosphorylation of JAK2 compared with tumors from KC mice with functional P

54 ted Janus kinase 1 (JAK1) or Janus kinase 2 (JAK2), concurrent with deletion of the wild-type allele.

55 itutive signaling driven by mutated FLT3 and JAK2 confers interchromosomal homologous recombination (

56 The JAK2V617F mutation, which renders JAK2 constitutively active and has been linked to myelop

57 STAT5-deficient mice, which was prevented by JAK2 deficiency and (ii) increased detoxification capaci

58 lectively, our findings show that macrophage JAK2 deficiency improves systemic insulin sensitivity an

59 Similar to GH(tg)STAT5(Deltahep) mice, JAK2 deficiency resulted in severe steatosis in the GH(t

60 e, we investigated the phenotypic effects of JAK2 deficiency.

61 Furthermore, using Jak2-deficient embryos, we demonstrate that Jak2 is cruc

62 The reduced oxidative damage in JAK2-deficient livers was linked to increased expression

63 nd (ii) increased detoxification capacity of JAK2-deficient livers, which diminished oxidative damage

64 Finally, overexpression of TFEB in JAK2-deficient podocytes reversed lysosomal dysfunction

65 Both male and female cardiac Jak2-deleted mice had hypertrophy, dilated cardiomyopath

66 ring a hepatocyte-specific deletion of JAK2 (JAK2(Deltahep)) to GH transgenic mice (GH(tg)) and compa

67 We demonstrate that PRL/JAK2-dependent phosphorylation of these tyrosines promot

68 The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the

69 AK1- and JAK3-dependent) and thrombopoietin (JAK2-dependent), demonstrating the high functional selec

70 We showed that JAK2 directly phosphorylates the N terminus of ninein wh

71 JAK2 E846D exhibited slightly stronger effects than JAK2

72 We propose that JAK2 E846D predominantly contributes to erythrocytosis,

73 membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness.

74 To determine whether the upstream kinase JAK2 exerts similar functions, we crossed mice harbourin

75 Mutations in JAK2 exon 12 are frequently found in patients with polyc

76 presses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutation found in PV patients.

77 Low JAK2-expressing rs10758669 AA macrophages were above thi

78 risk rs10758669 CC genotype showed increased JAK2 expression and nucleotide-binding oligomerization d

79 Interestingly, the threshold of JAK2 expression and signaling determined pattern-recogni

80 eased to increased secretion below a certain JAK2 expression threshold.

81 cytokines progressively decreased with lower JAK2 expression, proinflammatory cytokines switched from

82 We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations.

83 ipients, which facilitated evaluation of the JAK2/FLT3 inhibitor pacritinib in vivo.

84 pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibito

85 sence of JAK2V617F mutation, suggesting that JAK2-FOXO signaling has a different effect on progenitor

86 Therefore, blocking JAK2 function increases detoxifying GSTs in hepatocytes

87 ts of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of N

88 In contrast, patients with FGFR1 and JAK2 fusion TK genes exhibit a more aggressive course an

89 and PDGFRB) in 14.1%, EPOR rearrangements or JAK2 fusions in 8.8%, alterations activating other JAK-S

90 germline MPL-V285E mutation, and a germline JAK2-G571S variant.

91 JAK2 genetic variants are associated with inflammatory b

92 regulated in myeloid cells; consideration of JAK2 genotype and targeting of specific cell types might

93 ing mutations in known driver genes (DNMT3A, JAK2, GNAS, TET2, and ASXL1), including 196 point mutati

94 Mice in which JAK2 had been deleted from podocytes exhibited an elevat

95 LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell gro

96 PAX5-JAK2 has recently been identified as a novel recurrent f

97 The nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic

98 ular mechanisms underlying the regulation of JAK2 have remained elusive.

99 tions activating the JAK-STAT pathway (JAK1, JAK2, IL7R) identified in 63 patients (50.8% of those wi

100 Importantly, inhibition of Jak2 impairs tyrosine 78 phosphorylation and tumor growt

101 he entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF

102 ACs 1, 8, and 11, and >50-fold selective for JAK2 in a panel of 97 kinases.

103 Therefore, JAK2 in adipose tissue is epistatic to liver with regard

104 stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib imp

105 However, concomitant deletion of Jak2 in hepatocytes and adipocytes (JAK2LA) completely n

106 Finally, knocking down either MPL/TpoR or JAK2 in megakaryocytic progenitors from patients carryin

107 reveal a novel signaling axis that regulates JAK2 in normal and malignant HSPCs and suggest new thera

108 vations highlight the homeostatic actions of JAK2 in podocytes and the importance of TFEB to autophag

109 y addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammat

110 nt of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2" In addition to myeloproliferative neoplasms (MPN),

111 hat FED exerted its effects through multiple JAK2-independent mechanisms.

112 erent stimulation, and this was prevented by JAK2 inhibition in the OFC.

113 nd JAK2/STAT1-dependent manner, and specific JAK2 inhibition prevented PD-L1 upregulation in tumor ce

114 lated protein Arc, and this was prevented by JAK2 inhibition.

115 The JAK2 inhibitor AG490 given systemically or into the OFC

116 Lestaurtinib, a JAK2 inhibitor and one of the hits from the screen, repr

117 The JAK1/JAK2 inhibitor AZD1480 blocked the effect of cytokines o

118 r approach, we evaluated the investigational JAK2 inhibitor fedratinib (FED) in 64 patient samples.

119 The only approved JAK2 inhibitor for myelofibrosis is the dual JAK1 and JA

120 ice given a combination of gemcitabine and a JAK2 inhibitor formed smaller tumors and survived longer

121 abine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus cape

122 receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients

123 rden, after the introduction of the JAK1 and JAK2 inhibitor ruxolitinib.

124 bitor for myelofibrosis is the dual JAK1 and JAK2 inhibitor, ruxolitinib.

125 tudy, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy a

126 were given gemcitabine and a Janus kinase 2 (JAK2) inhibitor; tumor growth was monitored by 3-dimensi

127 JAK2 inhibitors also blocked C26 CM-induced STAT reporte

128 Janus kinase (JAK) 1/JAK2 inhibitors are in development or clinical use for i

129 oped as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem ce

130 ork for repurposing clinically approved JAK1/JAK2 inhibitors for type 1 diabetes.

131 Several other JAK2 inhibitors have entered clinical testing, but none

132 of which could successfully be combined with JAK2 inhibitors in the future.

133 The place of JAK2 inhibitors in the treatment of diffuse large B-cell

134 mphoma has not been defined; we suggest that JAK2 inhibitors might be most effective in poor prognosi

135 Although JAK2 inhibitors provide substantial clinical benefit, th

136 If approved, less myelosuppressive JAK2 inhibitors such as pacritinib or NS-018 could prove

137 ly or best available therapy (BAT) excluding JAK2 inhibitors until disease progression or unacceptabl

138 In addition, new JAK2 inhibitors with the potential for less myelosuppres

139 y of PAX5-JAK2 can be efficiently blocked by JAK2 inhibitors, rendering it a potential target for the

140 We also show for the first time that JAK2 is a direct BCL6 target gene; BCL6 bound to the JAK

141 , being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ fun

142 Jak2-deficient embryos, we demonstrate that Jak2 is crucially required for the function of the first

143 Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within

144 Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenit

145 harbouring a hepatocyte-specific deletion of JAK2 (JAK2(Deltahep)) to GH transgenic mice (GH(tg)) and

146 hormone (GH) signaling through disruption of Jak2 (JAK2L) leads to fatty liver.

147 were considered catalytically inactive, but JAK2 JH2 was found to have low autoregulatory catalytic

148 nein while the C terminus of ninein inhibits JAK2 kinase activity in vitro.

149 At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which p

150 is regulated through growth hormone-induced, JAK2 kinase-mediated phosphorylation of transcriptional

151 In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter activity, express

152 toneal macrophages from M-JAK2(-/-) mice and Jak2 knockdown in macrophage cell line RAW 264.7 also sh

153 ion of several of the genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated

154 -fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2(-/-)) mice gained less body weight

155 repression of the oncogenic kinases FLT3 and JAK2, leading to enhanced ERK and STAT3 signaling.

156 e latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3.

157 l inhibition and siRNA-mediated knockdown of Jak2 led to significant upregulation of Gst isoforms and

158 tol 3-kinase (Pi3k) signaling pathways, with Jak2 mainly relaying the proproliferation signaling, whe

159 MMB is not mediated by direct inhibition of JAK2-mediated ferroportin (FPN1) degradation, because ne

160 tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and

161 nt as the wild-type ligand, there is reduced JAK2-mediated phosphorylation of select downstream targe

162 Taken together, inhibiting Jak2-mediated tyrosine 78 phosphorylation could provide

163 t compared to wildtype littermate control (M-JAK2(+/+)) mice and were protected from HFD-induced syst

164 Peritoneal macrophages from M-JAK2(-/-) mice and Jak2 knockdown in macrophage cell lin

165 and chemokines in liver and VAT of HFD-fed M-JAK2(-/-) mice.

166 n visceral adipose tissue (VAT) of HFD-fed M-JAK2(-/-) mice.

167 eeding, macrophage-specific JAK2 knockout (M-JAK2(-/-)) mice gained less body weight compared to wild

168 in vivo BCL6 deficiency in DG75-AB7 induced JAK2 mRNA and protein expression and STAT3 phosphorylati

169 Activating JAK2 mutants cause hematological malignancies.

170 In PV mice that express the orthologous JAK2 mutation causing human PV, administration of minihe

171 Within the CRLF2(+) group, JAK2 mutation was associated with inferior outcomes.

172 tin production, bone marrow panmyelosis, and JAK2 mutation.

173 ith shorter survival than was the absence of JAK2 mutations (P=0.001), owing to a high risk of death

174 The role of somatic JAK2 mutations in clonal myeloproliferative neoplasms (M

175 a high risk of relapse, and the presence of JAK2 mutations was associated with shorter survival than

176 Recently, germ line JAK2 mutations were associated with polyclonal hereditar

177 udied a patient who inherited 2 heterozygous JAK2 mutations, E846D from the mother and R1063H from th

178 Polycythemia vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is d

179 Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed signific

180 Mice expressing the human JAK2-N542-E543del (Ex12) showed a strong increase in red

181 We generated a mouse model that expresses JAK2-N542-E543del, the most frequent JAK2 exon 12 mutati

182 Mutations in Janus kinase-2 (JAK2) occur in approximately 50% of patients.

183 individual roles of hepatocyte and adipocyte Jak2 on whole-body and tissue insulin sensitivity and li

184 rrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequ

185 tat3 in mice, or pharmacologic inhibitors of JAK2 or STAT3 activation, reduced fibrosis and the numbe

186 Genetic deletion of the tyrosine kinase JAK2 or the downstream transcription factor STAT5 in liv

187 Inhibition of gp130, Jak2, or Stat3 suppressed the formation of proliferating

188 The discovery of mutations in JAK2 over a decade ago heralded a new age for patient ca

189 ), abnormally activate the cytokine receptor/JAK2 pathway and their downstream effectors, more partic

190 rogram as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

191 Consistent with genetic deletion of Jak2, pharmacological inhibition and siRNA-mediated knoc

192 CIC stress decreased JAK2 phosphorylation in the OFC, and ketamine restored p

193 ide-binding oligomerization domain 2-induced JAK2 phosphorylation relative to AA carriers.

194 a direct BCL6 target gene; BCL6 bound to the JAK2 promoter in vitro and was enriched by ChIP-seq.

195 ed (CBL(mut) ) leukemias exhibited increased JAK2 protein levels and signaling and were hypersensitiv

196 ces in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations le

197 46D exhibited slightly stronger effects than JAK2 R1063H and caused prolonged EPO-induced phosphoryla

198 JAK2 R1063H, with very weak effect on JAK2/STAT5 signali

199 propose four novel MS genes, three of which (JAK2, REL, RUNX3) validated on the masked GWAS.

200 ted the efficacy and safety of fedratinib, a JAK2-selective inhibitor, in patients with ruxolitinib-r

201 Fedratinib, a JAK2-selective inhibitor, previously demonstrated clinic

202 L-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5

203 pathways, one of the most notable being the JAK2/signal transducer and activator of transcription 5

204 id leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1

205 ation, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as we

206 Deregulated JAK2 signaling has emerged as the central phenotypic dri

207 nating the regulation of both cell cycle and Jak2 signaling in HSCs.

208 2 inhibitor, because erythropoietin-mediated JAK2 signaling is essential for erythropoiesis.

209 However, hepatocyte autonomous JAK2 signaling regulates liver lipid deposition under co

210 ays revealed that the downstream mediator of JAK2 signaling STAT1 binds to the TFEB promoter.

211 nsactivation of Socs3, a potent inhibitor of Jak2 signaling, in cycling HSCs.

212 al activity, and is independent of canonical Jak2 signaling.

213 herapeutic vulnerability in LSCs with active JAK2 signaling.

214 ely regulating thrombopoietin (Tpo)-mediated Jak2 signaling.

215 k demonstrates how various tissues integrate JAK2 signals to regulate insulin/glucose and lipid metab

216 This ninein-dependent inhibition of JAK2 significantly decreases prolactin- and interferon g

217 er, in contrast to STAT5 deficiency, loss of JAK2 significantly delayed liver tumourigenesis.

218 In cultured podocytes, knockdown of JAK2 similarly impaired autophagy and led to downregulat

219 Overall, we identified the JAK2 SNP rs56118985 to be significantly associated with

220 L) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK

221 ants induce ligand-independent activation of JAK2/STAT/phosphatydylinositol-3'-kinase (PI3-K) and mit

222 ively, our findings suggest a novel role for JAK2/STAT1 in EGFR-mediated immune evasion, and therapie

223 g of the incoming capsid and depended on the JAK2/STAT1 pathway.

224 PD-L1 expression was induced in an EGFR- and JAK2/STAT1-dependent manner, and specific JAK2 inhibitio

225 Blockade of HGF/Met, Janus kinase 2 (JAK2)/STAT3 and TGF-beta1 signaling by specific inhibito

226 on the relative cell viability and the genes JAK2, Stat3, S6K, JUN, FOS, Myc, and Mcl1 are effective

227 tions and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

228 n of Bmi1 because of sustained activation of JAK2-STAT3 signaling downstream of p120-Kaiso-RhoA-ROCK

229 lves the activation of alpha7nAChR-dependent JAK2-STAT3 signaling pathway.

230 mors of mice, loss of P53 function activates JAK2-STAT3 signaling, which promotes modification of the

231 Further, Il-6 reinforced Jak2/Stat3 activation in SCPs and SCs.

232 patinib both in vitro and in vivo, including JAK2/STAT3 and hyaluronic acid.

233 implanted neuroblastoma cells, inhibition of JAK2/STAT3 and MEK/ERK/1/2 by ruxolitinib and trametinib

234 ed mice was dependent on the coactivation of JAK2/STAT3 and MEK/ERK1/2 in neuroblastoma cells.

235 Blockade of JAK2/STAT3 and TGF-beta signaling by specific inhibitors

236 VEGF rapidly stimulated VEGFR-2/JAK2/STAT3 binding and activated STAT3 to bind MYC and S

237 We then tested the role of JAK2/STAT3 in ketamine-induced plasticity in the OFC.

238 F-beta signaling inhibitor - SB431542 and/or JAK2/STAT3 inhibitor - JSI-124.

239 in receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor.

240 Therefore, we define an IL10RA/JAK2/STAT3 pathway each component of which is repressed

241 When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data sup

242 nesis and reduced osteogenesis by activating Jak2/Stat3 signaling in bone marrow stromal cells.

243 We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-i

244 ss-induced reversal learning deficit, and if JAK2/STAT3 signaling is involved in this effect.

245 These results suggest that the JAK2/STAT3 signaling pathway is a novel mechanism by whi

246 study demontrated that the TGF-beta and IL-6/JAK2/STAT3 signaling pathways form a positive feedback s

247 gamma) signaling and its downstream effector Jak2/Stat3, which are required for HSC formation, are ma

248 ms of RANKL through metalloproteases and the JAK2/STAT5 pathway, and it helps in restoring the decrea

249 3 increases membrane RANKL by activating the JAK2/STAT5 pathway.

250 n JAK2 V617F), and both weakly hyperactivate JAK2/STAT5 signaling only in the specific context of the

251 JAK2 R1063H, with very weak effect on JAK2/STAT5 signaling, is necessary to augment JAK2 activ

252 sed prolonged EPO-induced phosphorylation of JAK2/STAT5 via EPOR.

253 transducer and activator of transcription 5 (JAK2/STAT5), rat sarcoma/mitogen-activated protein kinas

254 via its cognate receptor and the downstream JAK2-STAT5a signalling pathway.

255 ntial thrombocythemia (ET) with mutations in JAK2, the thrombopoietin (TPO) receptor (MPL), and the c

256 echanism in which PI3K-deregulated p27 binds JAK2, to drive STAT3 activation and EMT through STAT3-me

257 JAK1 and JAK2 truncating mutations resulted in a lack of response

258 that depletion of CBL/CBL-B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanc

259 tive myeloproliferative neoplasms (MPNs) and JAK2 V617F clonal hematopoiesis in the general populatio

260 predisposition not only to MPN, but also to JAK2 V617F clonal hematopoiesis, a more common phenomeno

261 17F in a cell-intrinsic manner and prevented JAK2 V617F from up-regulating genes associated with prol

262 altered the transcriptional consequences of JAK2 V617F in a cell-intrinsic manner and prevented JAK2

263 P) array platform with custom probes for the JAK2 V617F mutation (V617F), we identified 497 individua

264 se agents is not restricted to patients with JAK2 V617F or exon 12 mutations.

265 stitutive signaling (albeit much weaker than JAK2 V617F), and both weakly hyperactivate JAK2/STAT5 si

266 TP binding ameliorate the hyperactivation of JAK2 V617F.

267 e beginning to understand better the role of JAK2(V617F) homozygosity, the function of comutations in

268 eta1) and Cxcl12 pathways in mice expressing Jak2(V617F) In addition, expression of Hmga2 causes upre

269 ate that expression of Hmga2 cooperates with Jak2(V617F) in the pathogenesis of MF.

270 oiesis, we transduced bone marrow cells from Jak2(V617F) knockin mice with lentivirus expressing Hmga

271 ted the development of MF in mice expressing Jak2(V617F) Mechanistically, the data show that expressi

272 tion and proliferation in the bone marrow of Jak2(V617F) mice, whereas TGF-beta1 or Cxcl12 stimulatio

273 nt mice as well as that in mice carrying the Jak2(V617F) mutation, thereby demonstrating the causal i

274 ents, and how these mutations cooperate with JAK2(V617F) to modulate MPN phenotype.

275 oxyurea was highly effective in vivo against JAK2(V617F)(+) murine MPN-like disease and also against

276 (+) murine MPN-like disease and also against JAK2(V617F)(+), CALR(del52)(+), and MPL(W515L)(+) primar

277 s in the hemopoietic stem cell, most notably JAK2(V617F), CALR, and MPL.

278 We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reac

279 loproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations.

280 ieve genome-wide significance when including JAK2(V617F)-positive cases.

281 N disease initiation potential compared with JAK2-V617F alone.

282 , including EZH2 In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contr

283 N) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes,

284 tions in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining c

285 Furthermore, EndMT is an early event in a JAK2-V617F knock-in mouse model of primary myelofibrosis

286 f Stat1 protein in bone marrow and spleen of JAK2-V617F mice after Stat3 deletion.

287 The acquired somatic JAK2-V617F mutation is present in >80% of patients with

288 In contrast, 1 patient with MF, a JAK2-V617F mutation, and MPO deficiency, carried 2 previ

289 h polycythemia vera (PV) that do not carry a JAK2-V617F mutation.

290 The MPN phenotype induced by JAK2-V617F was accentuated in JAK2-V617F;Ezh2(-/-) mice,

291 JAK2-V617F-expressing mice treated with an Ezh2 inhibito

292 lution transplantation with bone marrow from JAK2-V617F;Ezh2(+/-) mice showed increased reconstitutio

293 ype induced by JAK2-V617F was accentuated in JAK2-V617F;Ezh2(-/-) mice, resulting in very high platel

294 ive polymerase chain reaction (PCR) test for JAK2/V617F was negative.

295 We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations

296 5 (71%) of 35 molecular responders (with the JAK2 Val617Phe mutation) have maintained some response d

297 xamined how JAK signaling and IBD-associated JAK2 variants regulate distinct acute and chronic microb

298 JAK2 variants were identified in 5 of 57 triple-negative

299 Mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary hea

300 on, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 sig