ライフサイエンスコーパス: LSC

1 LSC activity at relapse was identified in populations of

2 LSC differentiation is associated with reversal of these

3 LSC maintenance is related, at least in part, to signals

4 LSC populations were identified using fluorescent-labele

5 LSCs are independent of BCR-ABL for survival, providing

6 LSCs home in bone marrow areas at low oxygen tension, wh

7 LSCs were first identified as rare cells with an immunop

8 LSCs, which are resistant to chemotherapy and serve as r

9 ng approach to selectively target inv(16)(+) LSCs.

10 We take La0.8Sr0.2CoO3 (LSC) as a model perovskite oxide, and modify its surface

11 esent a potential therapeutic target against LSCs.

12 viduals reveals two distinct clusters of AML LSC resembling either lymphoid-primed multipotent progen

13 the key scientific findings pertinent to AML LSC targeting and to consider methods of clinical evalua

14 p53 activity is inhibited in inv(16)(+) AML LSCs via interactions with the CBFbeta-SMMHC (CM) fusion

15 ce for DNA methylation variation between AML LSCs and their blast progeny, and identify epigeneticall

16 human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through th

17 as an effective strategy for eliminating AML LSCs.

18 targeting telomerase activity eradicates AML LSCs.

19 tics, and clinical associations of human AML LSCs and discuss critical questions that need to be addr

20 equired for engraftment of primary human AML LSCs and leukemogenesis, and it regulates LSC self-renew

21 ficantly inhibited JAK/STAT signaling in AML LSCs, and JAK inhibitors effectively inhibited FLT3-muta

22 aling through growth factor receptors in AML LSCs, including receptor tyrosine kinase c-KIT and FMS-r

23 tractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes.

24 levels were confirmed in human and mouse AML LSCs compared with hematopoietic stem cells (HSCs).

25 itors effectively inhibited FLT3-mutated AML LSCs.

26 inhibition for therapeutic targeting of AML LSCs.

27 These AML LSCs were shown to reside at the apex of a cellular hier

28 Here we show an LSC DNA methylation signature, derived from xenografts a

29 hematopoietic stem and progenitor aging and LSC generation remains unclear.

30 loss of Jagged-1 signals in altered HSC and LSC function after OB ablation.

31 noncoding RNAs in the regulation of HSC and LSC function and identify miR-99 as a critical regulator

32 front researchers working with human HSC and LSC in vivo.

33 ed AML before therapy and after relapse, and LSC frequency was assessed by limiting dilution analyses

34 mal transcription program shared by GMPs and LSCs.

35 nal complex that suppresses Egr1 in HSCs and LSCs.

36 was independently confirmed in both HSCs and LSCs.

37 R-99 regulates self-renewal in both HSCs and LSCs.

38 However, as LSCs often share features of lineage-restricted progenit

39 ant 3, containing variant exons 8-10, and BC LSC proliferation.

40 vides a pivotal opportunity for selective BC LSC detection and therapeutic elimination.

41 isis chronic myeloid leukemia stem cells (BC LSCs) was partially driven by decreased MBNL3.

42 (IL6) beta2SP(+/-) LSCs not only exhibited nuclear localization of Twist an

43 NFkappaB in (IL6) beta2SP(+/-) LSCs was activated by transforming growth factor beta (T

44 with interleukin-6 (pIL6; (IL6) beta2SP(+/-) LSCs) were highly tumorigenic and metastatic, whereas th

45 functional stem effects are opposite between LSC and HSC.

46 ew refined model of the relationship between LSCs and normal hemopoiesis in which the nature of genet

47 CD133(+) LSCs derived from preneoplastic livers of beta2SP(+/-) m

48 TAK1-NFkappaB signaling cascade in CD133(+) LSCs, and this program interacts with deficient TGFbeta

49 Within CD34(-) and CD34(+) LSC-containing populations, LSC frequencies are similar;

50 nhierarchically arranged CD34(+) and CD34(-) LSC populations.

51 CD34(-) LSCs have disordered global transcription profiles, but

52 CD36(+) LSCs have unique metabolic properties, are strikingly en

53 s and show that chemotherapy-resistant CD36+ LSCs co-opt gonadal adipose tissue to support their meta

54 Although human CD34(+)CD38(-) LSCs are generally highly quiescent, the C-type lectin C

55 compartment independent of the CD34(+)CD38(-)LSC phenotype.

56 erstanding human HSC and leukemia stem cell (LSC) biology and function in the context of a humanized

57 plantations and impaired leukemia stem cell (LSC) function.

58 Using publicly available leukemic stem cell (LSC) gene expression profiles and gene expression data g

59 ent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated.

60 he knowledge gained into leukemic stem cell (LSC) niche dependencies might be exploited to devise nov

61 d promote acquisition of leukemia stem cell (LSC) phenotypes.

62 fective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in trea

63 t transformation creates leukemic stem cell (LSC) populations arrested at a progenitor-like stage exp

64 c programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well

65 tabolic heterogeneity in leukemic stem cell (LSC) subpopulations and show that chemotherapy-resistant

66 , transforming it into a leukemic stem cell (LSC) that self-renews, proliferates, and differentiates

67 uster that characterizes leukemic stem cell (LSC)-depleted cells and a 25-gene cluster that character

68 represents a potential leukaemia stem cell (LSC)-directed therapy which may compliment tyrosine kina

69 sidered to be a facultative liver stem cell (LSC).

70 ts to identify the leukemia stem-like cells (LSC) have also indicated heterogeneity of these cells.

71 se most patients retain leukemic stem cells (LSC) and their progenitors in bone marrow and relapse fo

72 imited efficacy against leukemia stem cells (LSC) responsible for disease propagation, and most CML p

73 man acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA sig

74 ukemia do not eliminate leukemic stem cells (LSC).

75 TKI) fails to eliminate leukemia stem cells (LSC).

76 f-renewal of leukemia stem/initiation cells (LSCs/LICs).

77 elerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and

78 Limbal stem cells (LSCs) are affected globally and basal cell density could

79 Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance to B

80 Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and

81 Leukemia stem cells (LSCs) are resistant to current therapies used to treat c

82 Leukemia stem cells (LSCs) are thought to share several properties with hemat

83 that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a nich

84 HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny.

85 Leukemic stem cells (LSCs) drive progression of chronic myeloid leukemia (CML

86 typically distinguishes leukemic stem cells (LSCs) from normal hematopoietic stem cells (HSCs), and t

87 Leukemia stem cells (LSCs) have the capacity to self-renew and propagate dise

88 ial for the survival of leukemia stem cells (LSCs) in a murine model of BCR-ABL-induced chronic myelo

89 via the elimination of leukemia stem cells (LSCs) in mice.

90 into therapy-resistant leukemia stem cells (LSCs) in secondary acute myeloid leukemia (AML).

91 small number of MLL-AF9 leukemia stem cells (LSCs) in vivo.

92 n of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in prema

93 le of OBs in regulating leukemic stem cells (LSCs) is not well studied.

94 Eradication of leukemia stem cells (LSCs) is the ultimate goal of treating acute myeloid leu

95 nate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse.

96 d by subpopulations of leukaemia stem cells (LSCs) that are defined by their ability to engraft in im

97 s contain a population of limbal stem cells (LSCs) that continuously renew the corneal epithelium.

98 driven and sustained by leukemia stem cells (LSCs) with unlimited self-renewal capacity and resistanc

99 ncapable of eliminating leukemia stem cells (LSCs), suggesting that kinase-independent pathways suppo

100 but fails to eradicate leukaemic stem cells (LSCs), which maintain CML.

101 on but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are re

102 n by a rare fraction of leukemia stem cells (LSCs).

103 us in their capacity as leukemic stem cells (LSCs).

104 the eradication of CML leukemic stem cells (LSCs).

105 n of myeloid cells into leukemia stem cells (LSCs).

106 n of disease-initiating leukemic stem cells (LSCs).

107 ls and do not eliminate leukemic stem cells (LSCs).

108 radicate quiescent CML leukaemia stem cells (LSCs).

109 , due to persistence of leukemic stem cells (LSCs).

110 g the goal of targeting leukemic stem cells (LSCs).

111 c stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that

112 c stem cells [HSCs] and leukemic stem cells [LSCs]) that exceeds its function as a cell-cycle regulat

113 matopoietic stem cells, leukemic stem cells [LSCs], and leukemic blasts).

114 lls and a 25-gene cluster that characterizes LSC-enriched cells in parallel; both mark favorable-prog

115 , was an effective strategy to target CP-CML LSC.

116 se, and additional approaches to deplete CML LSC are needed to enhance the possibility of discontinui

117 ntified a molecular network critical for CML LSC survival and propose that simultaneously targeting t

118 ist (IL-1RA) inhibited IL-1 signaling in CML LSC and inhibited growth of CML LSC.

119 rexpression of inflammatory mediators in CML LSC, suggesting that blocking IL-1 signaling could modul

120 arker of CD34(+)/CD38( horizontal line ) CML LSC.

121 d in significantly greater inhibition of CML LSC compared with TKI alone.

122 signaling contributes to maintenance of CML LSC following TKI treatment and that IL-1 blockade with

123 m the BMM contributes to preservation of CML LSC following TKI treatment.

124 the number and self-renewal capacity of CML LSC in vitro.

125 aling in CML LSC and inhibited growth of CML LSC.

126 Here we show that the residual CML LSC pool can be gradually purged by the glitazones, anti

127 We show here that CML LSC demonstrated increased expression of the IL-1 recept

128 -1RA enhances elimination of TKI-treated CML LSC.

129 covery in patients almost 2 decades ago, CML LSCs have become a well-recognized exemplar of the cance

130 isms that promote the survival of the CP CML LSCs and how they can be a source of new gene coding mut

131 tifying therapeutic targets to eradicate CML LSCs may be a strategy to cure CML.

132 tein translation, selectively eradicates CML LSCs both in vitro and in a xenotransplantation model of

133 xpression of PRMT5 was observed in human CML LSCs.

134 we searched for such vulnerabilities in CML LSCs.

135 rdians of the quiescence and stemness of CML LSCs.

136 is PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with c

137 Strong evidence now shows that CML LSCs are resistant to the effects of TKIs and persist in

138 We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal.

139 vo self-renewal capacity of transplanted CML LSCs.

140 HSCs and chronic myelogenous leukemia (CML) LSCs.

141 ite the difficulties of identifying a common LSC phenotype, there is increasing evidence that high ex

142 nt thin-film luminescent solar concentrator (LSC) utilizing two pi-conjugated polymers as antennae fo

143 terials for luminescent solar concentrators (LSCs) as they can be engineered for providing highly tun

144 (SSC; 18,758 bp) and one large single copy (LSC; 89,132 bp).

145 activity by a liquid scintillation counter (LSC), the compounds can be quantified using gas chromato

146 using current liquid scintillation counting (LSC) techniques.

147 detection by liquid scintillation counting (LSC).

148 that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9- and

149 with genetically and phenotypically defined LSCs.

150 capacity of both murine and patient-derived LSCs.

151 for the H3K4 global methylome in determining LSC fate.

152 metabolic demands and survival of a distinct LSC subpopulation.

153 ortant mediator of MLL-AF9- and HOXA9-driven LSC function that is largely dispensable for HSC functio

154 ploration of anti-IL-1 strategies to enhance LSC elimination in CML.

155 rosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic myeloid leukaemia (CML

156 that approaches to treatment must eradicate LSCs for cure.

157 However, established LSCs lacking Hif-2alpha or both Hif-1alpha and Hif-2alph

158 On the basis of the estimated LSC properties, the patients can be divided into two pro

159 s uniquely found within the JAM-C-expressing LSC compartment.

160 ncreased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells.

161 acrophage progenitors (GMPs) is critical for LSC generation.

162 ycling, non-quiescent AML cells enriched for LSC activity.

163 yeloid differentiation is a prerequisite for LSC formation and AML development, providing insights fo

164 evelopment of AML, they are not required for LSC maintenance.

165 fication of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opp

166 ized doped CQWs are excellent candidates for LSCs.

167 e disease, although recipient mice do harbor LSCs.

168 e to repair the cornea by implanting healthy LSCs to encourage regeneration; however, success is limi

169 Nevertheless, high LSC self-renewal rate may partially compensate for slow

170 The results suggest that high LSC self-renewal and proliferation rates are indicators

171 How LSCs are maintained and differentiated into corneal epit

172 PR56) as a novel and stable marker for human LSCs for the majority of AML samples.

173 iptomics and network analyses--that in human LSCs, aberrantly expressed proteins, in both imatinib-re

174 and near elimination of transplantable human LSCs in mice, while sparing normal HSCs.

175 activity may not eradicate the most immature LSCs.

176 emical inhibition of 15-LO function impaired LSC function and attenuated CML in mice.

177 isoform switching and significantly impaired LSC maintenance.

178 Importantly, LSC subpopulations with myeloid and proliferative molecu

179 ntrols Src family kinase (SFK) activation in LSC and that LIC with exacerbated SFK activation was uni

180 BMPR1b expression and in BMP4 expression in LSC from TKI-resistant patients in comparison with diagn

181 iptional regulators previously implicated in LSC function.

182 We demonstrate a 9- to 90-fold increase in LSC frequency between diagnosis and relapse.

183 genetic protein (BMP) pathway is involved in LSC and progenitor expansion.

184 ive to explore the mechanisms that result in LSC survival and develop new therapeutic approaches.

185 rdered transcriptional program, resulting in LSC differentiation arrest at stages that are most like

186 In LSCs, p38alpha induces the expression of SDF-1, which ac

187 rtly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency.

188 w directions for deployment of doped CQWs in LSCs for advanced solar light harvesting technologies.

189 g-term culture-initiating cells (LTC-ICs) in LSCs from CML patients.

190 Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation,

191 GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the f

192 Preexisting gene expression programs in LSCs can be used to assess their transcriptional similar

193 esents a unique therapeutic vulnerability in LSCs with active JAK2 signaling.

194 used by corneal damage or disease, including LSC deficiency (LSCD).

195 Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven m

196 osine kinase (BCR-ABL1) antagonist inhibited LSC maintenance in a niche-dependent manner.

197 is drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with

198 y, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survi

199 te FLT3/internal tandem duplication (ITD)(+) LSCs.

200 es expression of let-7 and efficiently kills LSCs, providing an innovative therapeutic target in CML.

201 sity could be used as a parameter to measure LSC function at the early stages of the disease process.

202 lar to that observed in Msi2-deficent murine LSCs correlated with improved survival.

203 sease relapse requires identification of new LSC-selective target(s) that can be exploited therapeuti

204 es that accompany the evolution of these new LSC populations.

205 egies that aim at disrupting essential niche-LSC interactions or improve the regenerative ability of

206 hort (498-560 nm, SSC) and long (560-720 nm, LSC) spectral channels.

207 by accelerating the transformation of normal LSCs to metastatic cancer stem cells (mCSCs).

208 )and CD34(+)fractions, thus defining a novel LSC compartment independent of the CD34(+)CD38(-)LSC phe

209 encing technology with in vivo assessment of LSC frequencies and identified the adhesion G protein-co

210 nesis, reduced disease burden, and a loss of LSC function in a murine leukemia model.

211 n in leukemia development and maintenance of LSC function.

212 nregulation of Cited2, a master regulator of LSC quiescence.

213 le factor-1 (HIF-1), a critical regulator of LSC survival, on the maintenance of CML stem cell potent

214 and less reducible than Co on the B-site of LSC.

215 ent impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft

216 E and eliminate the self-renewal capacity of LSCs.

217 ition (EMT) and induces dedifferentiation of LSCs, which associate closely with expansion of basal an

218 ed myeloid differentiation, and depletion of LSCs.

219 s for selective targeting and eradication of LSCs.

220 s the first to characterize the evolution of LSCs in vivo after chemotherapy, identifying a dramatic

221 nsplants with sufficiently high fractions of LSCs, regardless of the LSC percentage in the donor tiss

222 arge number of LSCs, while a small number of LSCs required PAR-1 for their efficient growth.

223 liferation when there were a large number of LSCs, while a small number of LSCs required PAR-1 for th

224 at contain a sufficiently high percentage of LSCs.

225 ed here may enable the rapid purification of LSCs from a heterogeneous population of corneal cells, t

226 ulatory mechanism to control self-renewal of LSCs and indicates that PRMT5 may represent a potential

227 te leukemia through therapeutic targeting of LSCs without adverse effects on HSCs.

228 sights into the fundamental underpinnings of LSCs are now being made in an era in which drug developm

229 th refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improve

230 new curative therapeutic approaches based on LSC eradication.

231 tool compound antagonizes ADAR1's effect on LSC self-renewal in stromal co-cultures and restores let

232 trols efficient translation of the oncogenic LSC self-renewal program and suggest MSI2 as a potential

233 t 530 degrees C achieved by Hf addition onto LSC.

234 of high purity barium chloride, and optimize LSC counting parameters for (35)S determination in large

235 opulation capacity extends to BCR-ABL(p210+) LSCs.

236 haracterized leukemia stem cell populations (LSCs) from a well-defined cohort of patients with acute

237 4(-) and CD34(+) LSC-containing populations, LSC frequencies are similar; there are shared clonal str

238 ssion profiles of pretherapy and postrelapse LSCs were determined for published LSC markers.

239 Specifically, 2-ME2 abrogated pre-LSC viability and self-renewal activity in vivo by inhib

240 d to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis.

241 ic targeting of pre-leukemic stem cells (pre-LSCs) may be a viable strategy to eradicate residual dis

242 y cells in order to specifically monitor pre-LSCs, which were induced here by the SCL/TAL1 and LMO1 o

243 reening of compounds that target primary pre-LSCs maintained in a niche-like environment, on stromal

244 1 reduce ribosome biogenesis and provide pre-LSCs a selective advantage over normal hematopoietic cel

245 the development of strategies to target pre-LSCs that are absolutely dependent on their microenviron

246 Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemothera

247 But unlike mature precursors, LSCs express multiple normal stem cell transcriptional r

248 PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.

249 mbined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal commensurate with ADAR1 downregulation.

250 iation, and increase self-renewal of primary LSC in vivo.

251 as a potential target to eradicate primitive LSCs in AML.

252 stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally

253 mutagenesis data suggest that ADAR1 promotes LSC generation via let-7 pri-microRNA editing and LIN28B

254 AC8 aberrantly deacetylates p53 and promotes LSC transformation and maintenance.

255 ediated p53-inactivating mechanism promoting LSC activity and highlights HDAC8 inhibition as a promis

256 strelapse LSCs were determined for published LSC markers.

257 fficiencies that are comparable to published LSC techniques despite a 10-fold increase in the SO4 sam

258 ubstantial heterogeneity within the putative LSC population in CML at diagnosis and demonstrate diffe

259 ents of the MLL gene contain a non-quiescent LSC population.

260 F decreased leukemia development and reduced LSC maintenance.

261 ML LSCs and leukemogenesis, and it regulates LSC self-renewal predominantly by silencing CDKN2B, a ma

262 nic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lip

263 ription factor highly expressed in resistant LSC.

264 omplete cytogenetic remission, TKI-resistant LSC and progenitors display high levels of BMPR1b expres

265 logical properties of chemotherapy-resistant LSCs, a cellular entity of prime clinical importance, wi

266 correlated to JAM-C expression that reveals LSC heterogeneity.

267 ecords of patients with medically reversible LSC disease were reviewed.

268 tivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly co

269 newal rate may partially compensate for slow LSC proliferation and vice versa.

270 CQDs that are aimed for full solar spectrum LSCs suffer from moderately low quantum efficiency, intr

271 be most effective for identifying successful LSC-directed therapies.

272 ing that kinase-independent pathways support LSC survival.

273 rehensive epigenetic landscape that sustains LSC cellular identity and functionality is less well est

274 rmining the best strategy by which to target LSCs, with their well-documented heterogeneity and readi

275 tification of molecules capable of targeting LSCs appears therefore of primary importance to aim at C

276 on medicine strategy providing evidence that LSCs can be eradicated.

277 We report that LSCs in MLL-associated leukemia reside in an epigenetic

278 The LSC epigenetic signature is associated with poor prognos

279 The LSC exhibits high photoluminescence quantum yield, low r

280 gulation of crucial MLL target genes and the LSC maintenance transcriptional program that is driven b

281 pproaches that show promise to eradicate the LSC, and future challenges on the path to cure.

282 ling approach has enabled us to estimate the LSC properties of 31 individuals with relapsed AML and t

283 reducing the concentration of and making the LSC more oxidized at its surface.

284 The most TKI-insensitive cells of the LSC compartment can be captured within the CD45RA(-) fra

285 ly high fractions of LSCs, regardless of the LSC percentage in the donor tissue.

286 ed by the poorly understood signature of the LSC phenotype.

287 proliferation and self-renewal rates of the LSC population have greater impact on the course of dise

288 A Monte Carlo simulation predicts the LSC to possess exceptionally high optical efficiencies o

289 non-cell-autonomous therapies targeting the LSC niche.

290 lysis to define the heterogeneity within the LSC population in chronic phase chronic myeloid leukemia

291 s a new and novel method for eliminating the LSCs that are otherwise not targeted by existing therapi

292 ted whether hypoxia similarly contributes to LSC persistence.

293 tion, tightly coupling miR-126 expression to LSC function.

294 ve contribution of differentiation status to LSC transformation is unclear.

295 that inhibition of telomerase is damaging to LSCs and may represent a promising therapeutic approach

296 agate AML with the same latency as wild-type LSCs.

297 issecting the molecular machinery underlying LSC self-renewal.

298 acterized by the confluence of understanding LSCs and the ability to target them, is shifting from "i

299 form biomarkers of healthy HSPC aging versus LSC generation, may be employed safely and effectively t

300 ved from WT mice treated with pIL6 ((IL6) WT LSCs) had significantly less proliferation and no tumori