ライフサイエンスコーパス: CSF1R

1 CSF1R is a representative of this signature, and its exp

2 CSF1R was not upregulated in hTERT immortalized epitheli

3 CSF1R(+) myeloid-primed embryonic ProB cells are relevan

4 (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proli

5 ison to insulin in 3T3-L1 cells expressing a CSF1R/IR mutated at Tyr960 (CSF1R/IRA960).

6 Here, we show that application of a CSF1R inhibitor eliminated virtually all microglia from

7 the 25 d lesion, we administered PLX3397, a CSF1R inhibitor, for 30 d to eliminate microglia.

8 Moreover, microglial depletion with a CSF1R antagonist prior to stress prevented the recruitme

9 human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to das

10 lude ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alteration

11 ed targetable ABL-class fusions (ABL1, ABL2, CSF1R, and PDGFRB) in 14.1%, EPOR rearrangements or JAK2

12 Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-ind

13 ollow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticoba

14 s and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1 The over 1,000 genetic alteration

15 Here we investigated whether an alternative CSF1R ligand, interleukin 34 (IL-34), is responsible for

16 mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R.

17 Gene expression of CD68, CD11b, and CSF1R but not Mphi was correlated negatively with glucos

18 e-specific gene expression (CD68, CD11b, and CSF1R), were correlated with percent body fat, age, and

19 human breast tumors expressing both CSF1 and CSF1R, invasion in vivo is dependent both on a paracrine

20 increased inflammatory cell recruitment and CSF1R signal transduction in both macrophages and endoth

21 As CSF1R is a crucial mediator of microglial proliferation

22 As CSF1R regulates microglia this mutation implies that dys

23 Abrogation of autocrine CSF1R signaling in MDA-MB-231 xenografts (a claudin-low

24 Our results suggest that autocrine CSF1R signaling is essential in maintaining low claudin

25 n about the mechanism by which the autocrine CSF1R signaling contributes to tumor progression.

26 te enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL

27 aded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred.

28 ny stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS.

29 artly caused by the monocytopenia induced by CSF1R inhibition.

30 ion and invasion are oppositely regulated by CSF1R downstream of TGFbeta only in claudin-low cell lin

31 th typical features of ALSP who do not carry CSF1R mutations.

32 factor-1 receptor/insulin receptor chimera (CSF1R/IR)) connecting the extracellular, ligand-binding

33 factor-1 receptor/insulin receptor chimera (CSF1R/IR).

34 Combining CSF1R inhibitor with a CXCR2 antagonist blocked granuloc

35 rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 a

36 93A) mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS.

37 Our results highlight the importance of CSF1/CSF1R signaling in the recruitment of TIMs that can limi

38 o acid deletion of the juxtamembrane domain (CSF1R/IRDelta960).

39 Finally, although both elevated CSF1R and IL-4Ralpha signaling triggered proliferation a

40 These early embryonic CSF1R(+)CD19(+) ProB cells also express multiple other m

41 of coincident expression with the endogenous CSF1R protein.

42 cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effec

43 eurons in the hippocampus and cortex express CSF1R under physiological conditions and that kainic aci

44 ific sensitivity to down-regulation of FLT1, CSF1R, PDGFR, ROR1, EPHA4/5, JAK1/3, LMTK3, LYN, FYN, PT

45 eukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presentin

46 esent in CSF1-deficient mice but absent from CSF1R-deficient mice.

47 ce analysis of cDNA generated by 5'RACE from CSF1R coding sequences identified a novel fusion of the

48 e Colony-Stimulating Factor 1 Receptor gene (CSF1R).

49 ue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation

50 crosstalk enforces aggressive CD44(+)IGF1R(+)CSF1R(+) LC phenotypes, including extranodal invasion an

51 and immune cell differentiation (eg, IL10RA, CSF1R) decreased.

52 DNA from this subject displayed chimerism in CSF1R acquired after haematopoietic stem cell transplant

53 d a novel, heterozygous missense mutation in CSF1R [c.1990G > A p.(E664K)] by exome sequencing in fiv

54 We identified 12 probands with mutations in CSF1R.

55 is a novel monoclonal antibody that inhibits CSF1R activation.

56 by Western blotting revealed that the intact CSF1R/IR co-precipitates with IRS-2 from CSF-1-treated c

57 brain injury and neurodegeneration involving CSF1R expression on neurons.

58 in the juxtamembrane region of the CSF1R/IR (CSF1R/IRDelta960) blocked CSF-1-stimulated phosphorylati

59 y other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulatio

60 To determine whether the other known CSF1R ligand IL34 is expressed in gliomas, we examined e

61 Phosphopeptide maps of the 32P-labeled CSF1R/IR protein revealed the same pattern of phosphoryl

62 As in mammals, CSF1R-reporter genes were specifically expressed at high

63 of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle micro

64 he kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss

65 ent to initiate involution in the absence of CSF1R(+) macrophages.

66 y the pathway regulated by the activation of CSF1R and the transcription factors PU.1 and C/EBPalpha

67 We show that targeting the activity of CSF1R inhibits microglial proliferation and slows neuron

68 Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1

69 We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway pr

70 Selective deletion of CSF1R in forebrain neurons in mice exacerbated excitotox

71 Depletion of CSF1R(+) macrophages resulted in delayed mammary involut

72 the cleavage of the intracellular domain of CSF1R.

73 Downstream of CSF1R, we found that the microglial membrane adaptor pro

74 ied the mechanism that limited the effect of CSF1R targeted therapy.

75 s provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer's disease, and v

76 's disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported.

77 genic mice correlates with the expression of CSF1R and its ligand CSF1.

78 r, we described increased mRNA expression of CSF1R in human telomerase reverse transcriptase (hTERT)

79 Reducing the expression of CSF1R using short hairpin interfering RNA abolished thes

80 e have significantly increased expression of CSF1R.

81 sults give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and

82 These data highlight the importance of CSF1R signaling in the recruitment and function of disti

83 systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline i

84 Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine ki

85 tiphoton imaging revealed that inhibition of CSF1R in the tumor cells leads to decreased in vivo moti

86 Inhibition of CSF1R using small molecule inhibitors such as imatinib,

87 hages by an orally administered inhibitor of CSF1R may offer a highly efficacious and safe treatment

88 use the selective pharmacologic inhibitor of CSF1R signaling, GW2580, to demonstrate that CSF-1 regul

89 ed to radiotherapy, a selective inhibitor of CSF1R suppressed tumor growth more effectively than irra

90 mpletely blocked by a selective inhibitor of CSF1R.

91 l cell lines showed rapid internalization of CSF1R with concomitant down-modulation and colocalizatio

92 pulation in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth

93 ng that HDLS may result from partial loss of CSF1R function.

94 verexpress CSF1, resulting in recruitment of CSF1R-bearing macrophages that are polyclonal and make u

95 SF1R) activation leads to the recruitment of CSF1R-expressing cells of the mononuclear phagocyte line

96 d macrophages and an autocrine regulation of CSF1R in the tumor cells themselves.

97 eficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis.

98 However, the role of CSF1R signaling in microglial homeostasis in the adult b

99 A combined score of CSF1R in situ hybridization and CD68 immunohistochemistr

100 uencing in a family and Sanger sequencing of CSF1R.

101 Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performanc

102 in ALS, supporting therapeutic targeting of CSF1R in this disease.

103 Use of CSF1R inhibitors to target TAM is therapeutically appeal

104 heimer's disease brain are also dependent on CSF1R signalling, and if so, how these cells contribute

105 Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metas

106 evidence of ALSP who do not carry pathogenic CSF1R mutations.

107 whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential ben

108 Expression of the RBM6-CSF1R fusion protein conferred interleukin-3 (IL-3)-inde

109 naling by the myeloid growth factor receptor CSF1R can functionally reprogram macrophage responses th

110 ia/macrophage cytokine CSF1 and its receptor CSF1R are overexpressed in human high-grade gliomas.

111 in the colony stimulating factor-1 receptor (CSF1R) gene.

112 in the colony stimulating factor 1 receptor (CSF1R) have recently been discovered as causal for hered

113 The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid lineage cells.

114 ophage colony-stimulating factor 1 receptor (CSF1R) is a product of the proto-oncogene c-fms and a me

115 ingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation

116 ivated colony-stimulating factor 1 receptor (CSF1R) kinase in the acute megakaryoblastic leukemia (AM

117 of the colony stimulating factor 1 receptor (CSF1R) locus.

118 eptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C-C motif) receptor 2 (CCR2) decrea

119 ent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in the healthy adult brain

120 CSF-1 receptor (CSF1R) signaling is important for the recruitment of CD1

121 end on colony-stimulating factor 1 receptor (CSF1R) signalling for survival, and pharmacological inhi

122 22) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia post-irradiation.

123 essing colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning in the Mafia

124 of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for

125 ss the colony-stimulating factor-1 receptor (CSF1R), previously thought to be expressed, and play a l

126 of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the pro

127 of the colony stimulating factor 1 receptor (CSF1R).

128 urvival pathway we used a chimeric receptor (CSF1R/IR) consisting of the ligand-binding domain of the

129 A chimeric receptor (CSF1R/IRDelta960) with a deletion of 12 amino acids from

130 CSF1 receptor (CSF1R) activation leads to the recruitment of CSF1R-expr

131 are functional ligands of the CSF1 receptor (CSF1R) and thus are key regulators of the monocyte/macro

132 re it targeted the microglial CSF1 receptor (CSF1R).

133 ment of therapy targeting the CSF1 receptor (CSF1R).

134 A chimeric growth factor receptor (CSF1R/IR) was constructed by splicing cDNA sequences enc

135 timulating factor-1 (CSF1) and its receptor (CSF1R) have critical roles during breast cancer progress

136 tors of CSF1 signaling through its receptor, CSF1R, were tested in combination with ABT, demonstratin

137 res the growth factor CSF1 and its receptor, CSF1R.

138 old 5xfAD mice were treated with a selective CSF1R inhibitor for 1 month, resulting in the eliminatio

139 Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation i

140 this end, we tested the effects of selective CSF1R inhibitors on microglia in adult mice.

141 y research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the a

142 athobiology of treatment failure and suggest CSF1R as a drug target of at-risk CHL.

143 DSCs, and validate the benefits of targeting CSF1R signaling in combination with antiangiogenic drugs

144 Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis

145 of breast cancer cell lines, we confirm that CSF1R expression is elevated and regulated by TGFbeta sp

146 Here, we further describe that CSF1R is upregulated at both the mRNA and protein level

147 The discovery that CSF1R mutations cause ALSP led to more accurate prognosi

148 We estimate that CSF1R mutations account for 10% of idiopathic adult onse

149 Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central a

150 nvestigations of this response revealed that CSF1R blockade also upregulated T-cell checkpoint molecu

151 A and a small-molecule inhibitor showed that CSF1R is essential for the growth and survival of MKPL-1

152 Our study shows that CSF1R mutations are responsible for a significant propor

153 the basis of these findings, we suggest that CSF1R may be a critical factor facilitating hTERT immort

154 The CSF1R and AARS2 proteins have different cellular functio

155 Upon activation with CSF-1, the CSF1R/IR phosphorylates itself and intracellular substra

156 the CSF1R/IRDelta960 was as effective as the CSF1R/IR in mediating CSF-1 protection of cells from sta

157 Upon stimulation by the CSF1R ligand CSF1, the immortalized epithelial cell line

158 In contrast, the CSF1R/IRA960 co-precipitates poorly with IRS-2.

159 ition of apoptosis, activation of either the CSF1R/IR or the CSF1R/IRDelta960 rapidly induced membran

160 ylinositol 3' kinase in cells expressing the CSF1R/IR but not in cells expressing the CSF1R/IRDelta96

161 te-1 (IRS-1) and Shc in cells expressing the CSF1R/IR chimera.

162 F-1 treatment protected cells expressing the CSF1R/IR from staurosporine-induced apoptosis.

163 CSF-1-treated adipocytes expressing the CSF1R/IRA960 were impaired in their ability to phosphory

164 CSF-1-treated cells expressing the CSF1R/IRDelta960 are unable to phosphorylate IRS-1 and S

165 the CSF1R/IR but not in cells expressing the CSF1R/IRDelta960.

166 other's blood and saliva were mosaic for the CSF1R mutation.

167 aused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene.

168 s and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencep

169 nd AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gen

170 Genetic loss of the CSF1R blocks the normal population of resident microglia

171 mma to inhibit expression of RANK and of the CSF1R gene that encodes c-Fms, and to synergistically in

172 it has been known since the discovery of the CSF1R gene that there are patients with typical clinical

173 Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactiv

174 However, the impact of the CSF1R signaling pathway on other TIM subsets, including

175 n line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with

176 etion within the juxtamembrane region of the CSF1R/IR (CSF1R/IRDelta960) blocked CSF-1-stimulated pho

177 The anti-apoptotic action of the CSF1R/IRDelta960 was reversed by dominant-inhibitory Rac

178 is, activation of either the CSF1R/IR or the CSF1R/IRDelta960 rapidly induced membrane ruffling in Ra

179 In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greec

180 Surprisingly, the CSF1R/IRDelta960 was as effective as the CSF1R/IR in med

181 chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AML1 (CBF

182 nt differentiation when transfected with the CSF1R/IR chimera cDNA but not when transfected with the

183 ition of CSF-1 to cells transfected with the CSF1R/IR chimera cDNA stimulated the tyrosine phosphoryl

184 Notably, these CSF1R(+) myeloid-primed ProB cells are uniquely present

185 strate that elimination of microglia through CSF1R inhibition can ameliorate radiation-induced cognit

186 such inhibitors and monoclonal antibodies to CSF1R are putative drugs that may play an important role

187 on of the RNA binding motif 6 (RBM6) gene to CSF1R gene generated presumably by a t(3;5)(p21;q33) tra

188 indings suggest that expression of wild-type CSF1R in some cells, whether achieved by mosaicism or ch

189 lls expressing a CSF1R/IR mutated at Tyr960 (CSF1R/IRA960).

190 ult brain are physiologically dependent upon CSF1R signaling.

191 multiple recurrences, systemic therapy using CSF1R inhibitors may help delay or avoid surgical proced

192 We show that, both in vitro and in vivo, CSF1R inhibition results in a reversal of claudin-low ma

193 phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported.

194 ogic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequenci

195 growth, but that combining these agents with CSF1R blockade potently elicited tumor regressions, even

196 The few recently reported families with CSF1R mutations had been previously labelled "hereditary

197 Treatment with CSF1R inhibitors disrupted this crosstalk and triggered

198 ms intronic regulatory element (FIRE) within CSF1R is shown to be highly conserved in amniotes and ab