ライフサイエンスコーパス: AML

1 AML exosomes reprogram NK-92 cells, interfering with the

2 AML patient samples with FLT3-ITD express high levels of

3 AML that arises after RAI treatment has a poor prognosis

4 AML, similar to most other cancers, is characterized by

5 developed a hematopoietic neoplasm (4 MDS, 1 AML, 1 MPN, and 2 MDS/MPN) and 3 patients (1.1%) develop

6 genome-scale short hairpin RNA screens in 17 AML cell lines and analyzed dependencies relative to par

7 We analyzed 57 AML patients with normal karyotype by using Illumina's 4

8 the underlying aggressive pathobiology in -7 AML patients.

9 In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes

10 Hereby, we advocate assessment of adult AML with respect to coexisting p53 alterations.

11 stem cell functions, its aberrations affect AML evolution, biology, and therapy response and usually

12 up98 fusion protein implicated in aggressive AML causes mislocalization of H3K4me3 at abnormal region

13 tion, CX-5461, effectively treats aggressive AML, including mixed-lineage leukemia-driven AML, and ou

14 Although virtually all AMLs with wild-type DNMT3A displayed CpG island hypermet

15 g and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling.

16 growth arrest, and prolonged survival in an AML mouse model.

17 n of carnitine palmitoyltransferase IA in an AML patient-derived xenograft model improves survival.

18 ic/molecular risks could be combined into an AML composite model that could guide treatment decision-

19 isions and differentiation in AML blasts and AML stem/progenitor cells, inhibited cell growth and col

20 against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusio

21 Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients.

22 to contribute to the pathogenesis of MDS and AML.

23 WHO classification of myeloid neoplasms and AML, and mutations in three genes- RUNX1, ASXL1, and TP5

24 isional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been included in the current up

25 s, suggesting that hypomethylation antedates AML.

26 pression analysis of The Cancer Genome Atlas AML data set reveals that GLI3 expression is silenced in

27 tween AML blasts and BM-MSCs, which benefits AML proliferation and survival.

28 Here, we report a novel interaction between AML blasts and BM-MSCs, which benefits AML proliferation

29 of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago throug

30 To systematically characterize AML's genetic dependencies, we conducted genome-scale sh

31 ounts for 4-15% of newly diagnosed childhood AML cases.

32 erall pattern in AML, those patients with CN-AML have a poorer survival rate when GFI1 expression is

33 of Cdc42 resulted in a shift to depolarized AML cells that is associated with a decrease in the freq

34 lines, induced apoptosis in patient-derived AML samples in vitro and led to a 2-log reduction in the

35 AI had an increased early risk of developing AML and CML but no other hematologic malignancies.

36 to 59 years of age, who had newly diagnosed AML for FLT3 mutations.

37 lowed us to study the properties of distinct AML subclones, including differential drug susceptibilit

38 c Nras signaling to transform MEPs and drive AML development.

39 eukemia development in an NUP98-HOXA9-driven AML model.

40 AML, including mixed-lineage leukemia-driven AML, and outperforms standard chemotherapies.

41 BP4 increases survival in Hoxa9/Meis1-driven AML model.

42 y longer with Npm1(cA/+);Nras(G12D/+) During AML evolution, both models acquired additional copies of

43 Endosteal AML cells produce pro-inflammatory and anti-angiogenic c

44 ombined inhibition, is sufficient to enhance AML drug sensitivity, which provides a novel therapeutic

45 Two new provisional entities, AML with mutated RUNX1 and AML with BCR- ABL1, have been

46 Confirming miR-99's role in established AML, miR-99 inhibition induced primary AML patient blast

47 irst drug to receive regulatory approval for AML in the United States since the year 2000.

48 therapies that are currently considered for AML.

49 linking two major prognostic indicators for AML.

50 The expression levels of some markers for AML subtypes and c-MYC regulated genes were considered p

51 017 European LeukemiaNet recommendations for AML.

52 ch provides a novel therapeutic strategy for AML treatment.

53 eath within 1 year after initial therapy for AML.

54 he most effective single agent treatment for AML.

55 identifying appropriate patients for future AML trials of ADI-PEG20.

56 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS.

57 Human AML cells from terminally ill mice treated with chemothe

58 Screens in both human AML and engineered mouse pro-B cells converge on a surpr

59 mined the cytokine profile in cultured human AML compared with AML cultured with BM-MSCs and found th

60 RALB-dependent antileukemic effects in human AML cell lines, induced apoptosis in patient-derived AML

61 genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be

62 anistic basis and clonal properties of human AML.

63 2D/+) mice showed acquisition of other human AML mutations, including IDH1 R132Q.

64 inducible CDC42 suppression in primary human AML cells blocks leukemia progression in a xenograft mod

65 Knock-down of GFI1 expression in the human AML Fujioka cell line led to a decrease in the level of

66 Using a humanized AML model, we demonstrate that upregulation of GFI1 expr

67 hermore, contrary to the Warburg hypothesis, AML relies on oxidative phosphorylation to generate aden

68 hRNA or small-molecule inhibition of PU.1 in AML cells from either PU.1lo mutant mice or human patien

69 ing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML.

70 ddC was preferentially activated in AML cells compared with normal hematopoietic progenitor

71 sm of escape from NRAS oncogene addiction in AML.

72 Current advances in AML research yield important insights regarding AML gene

73 cked the drug-sensitizing effect of ALOX5 in AML cells.

74 the therapeutic effect of SMO antagonists in AML samples and restoration of GLI3R suppresses the grow

75 dings support evaluation of this antibody in AML therapy, with particular appeal to patients resistan

76 les-potentiates the cytotoxicity of Ara-C in AML cells.

77 ibition alone or combined with cytarabine in AML cells.

78 re that SAMHD1 reduces Ara-C cytotoxicity in AML cells.

79 nducing DNA replication stress and damage in AML cell lines.

80 PHK1 induced caspase-dependent cell death in AML cell lines, primary AML patient blasts, and isolated

81 reatment decision-making and trial design in AML.

82 errations that govern disease development in AML.

83 metric cell divisions and differentiation in AML blasts and AML stem/progenitor cells, inhibited cell

84 pression as a mechanism for immune escape in AML and MDS.

85 Novel recurrent mutational events in AML were identified in the SMARCA2 gene.

86 ings identify elevation of A3A expression in AML cells, enabling apoptotic sensitivity to inhibitors

87 Overexpression of GLI1 in AML cells led to increased AKT phosphorylation and decre

88 y primary AML, and that IL8 was increased in AML/BM-MSC cocultures.

89 itor AZ20 caused proliferation inhibition in AML cell lines and primary patient samples.

90 of apoptosis and proliferation inhibition in AML cell lines.

91 he STAT/TET1 axis by selective inhibitors in AML treatment.

92 oma-induced resistance to BCL2 inhibitors in AML.

93 with MLL fusion proteins and is involved in AML, however, its functions are not well understood.

94 c nucleoside kinases reduced mtDNA levels in AML cells, demonstrating their contribution in maintaini

95 ential target to eradicate primitive LSCs in AML.

96 egulation and targeting histone methylome in AML together with the success in developing lead compoun

97 Unlike the overall pattern in AML, those patients with CN-AML have a poorer survival r

98 ectively target oxidative phosphorylation in AML.

99 CLL-1 is prevalent in AML and, unlike other targets such as CD33 and CD123, is

100 ll gene signatures predict poor prognosis in AML patients; however, with few exceptions, these deregu

101 ression has been linked to poor prognosis in AML.

102 the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhi

103 lications for these small regulatory RNAs in AML.

104 emia and suggest its broader significance in AML.

105 transfer as a novel therapeutic strategy in AML.

106 is associated with worse overall survival in AML.

107 algorithm for p53-based diagnostic workup in AML is presented, aiming at facilitating the p53-based t

108 gene silencing and was essentially absent in AMLs with DNMT3A(R882) mutations.

109 ypomethylation is an initiating phenotype in AMLs with DNMT3A(R882), while DNMT3A-dependent CpG islan

110 to prevent mitochondrial transfer, increase AML apoptosis, and improve NSG AML mouse survival.

111 t with recombinant S100A9 proteins increased AML cell maturation, induced growth arrest, and prolonge

112 the loss of Cdc42 abrogates MLL-AF9-induced AML development.

113 ibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression

114 targeted IL8 shRNA inhibited BM-MSC-induced AML survival.

115 initiating cells and are capable of inducing AML in serially transplanted recipients.

116 es, primary AML patient blasts, and isolated AML patient leukemic progenitor/stem cells, with negligi

117 d confirmed high HHEX expression in FLT3-ITD AMLs.

118 urther, inhibition of miR-155 in FLT3-ITD(+) AML cell lines using CRISPR/Cas9, or primary FLT3-ITD(+)

119 nd is critical for the growth of FLT3-ITD(+) AML cells in vitro.

120 ur observations in mice, primary FLT3-ITD(+) AML clinical samples have significantly higher miR-155 l

121 is specifically overexpressed in FLT3-ITD(+) AML compared with FLT3 wild-type (FLT3-WT) AML and is cr

122 es using CRISPR/Cas9, or primary FLT3-ITD(+) AML samples using locked nucleic acid antisense inhibito

123 ibited survival of primary human FLT3/ITD(+) AML cells compared to FLT3/ITD(neg) cells and spared nor

124 from patients with acute myeloid leukaemia (AML) and induce the differentiation of RA-low sensitive

125 s in bone marrow of acute myeloid leukaemia (AML) patients, and the complex immune response in blood

126 syndromes (MDS) and acute myeloid leukaemia (AML).

127 iatric and adult acute myelogenous leukemia (AML).

128 activity against acute myelogenous leukemia (AML).

129 Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes.

130 s from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL).

131 erogeneous nature of acute myeloid leukemia (AML) and its poor prognosis necessitate therapeutic impr

132 osides used to treat acute myeloid leukemia (AML) and other cancers remains a major obstacle to clini

133 erapeutic target for acute myeloid leukemia (AML) and other forms of cancer.(1-4) The nature and exis

134 mary patient-derived acute myeloid leukemia (AML) and other hematologic malignancies such as myelofib

135 or cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21) and i

136 Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis

137 Acute myeloid leukemia (AML) cells have increased mitochondria compared with non

138 Adults with acute myeloid leukemia (AML) commonly require support in the intensive care unit

139 ients diagnosed with acute myeloid leukemia (AML) die of their disease.

140 lderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance t

141 nduction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and surv

142 studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA exp

143 In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening

144 Acute myeloid leukemia (AML) is a disease associated with epigenetic dysregulati

145 Acute myeloid leukemia (AML) is a major unmet medical need.

146 Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instabil

147 val of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related t

148 in preclinical human acute myeloid leukemia (AML) models at the cost of severe hematologic toxicity.

149 d in the majority of acute myeloid leukemia (AML) patients.

150 ith a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS dif

151 r many patients with acute myeloid leukemia (AML) remain dismal.

152 MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse

153 nalysis of 542 human acute myeloid leukemia (AML) samples and identified 55% with upregulated mtDNA b

154 tic abnormalities to acute myeloid leukemia (AML) should assist integrated design of targeted therapi

155 erapeutic targets in acute myeloid leukemia (AML) that are of great current interest.

156 graft model of human acute myeloid leukemia (AML) that enabled chemotherapy-induced regressions of es

157 T3) is a hallmark of acute myeloid leukemia (AML) that harbors the FLT3-internal tandem duplication (

158 refractory/poor-risk acute myeloid leukemia (AML) was evaluated in 43 patients in a prospective, phas

159 lapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to

160 urpose Children with acute myeloid leukemia (AML) whose disease is refractory to standard induction c

161 N are predisposed to acute myeloid leukemia (AML), and progression from SCN to AML is accompanied by

162 highly expressed in acute myeloid leukemia (AML), and S100A8 expression has been linked to poor prog

163 FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a distinct entity

164 neoplasms, including acute myeloid leukemia (AML), has been greatly advanced by genomics discovery st

165 spectively), but not acute myeloid leukemia (AML), in mouse models of these tumors.

166 riggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin lymphoma, and multiple myeloma cells.

167 ignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be req

168 sis in patients with acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia, and myelodysp

169 Acute myeloid leukemia (AML), the most common adult acute leukemia in the United

170 In acute myeloid leukemia (AML), therapy resistance frequently occurs, leading to h

171 ic syndrome (MDS) or acute myeloid leukemia (AML).

172 ch for patients with acute myeloid leukemia (AML).

173 models of refractory acute myeloid leukemia (AML).

174 ted in patients with acute myeloid leukemia (AML).

175 n is associated with acute myeloid leukemia (AML).

176 al oncogenic role in acute myeloid leukemia (AML).

177 signals in high risk acute myeloid leukemia (AML).

178 myeloid diseases to acute myeloid leukemia (AML).

179 ounger patients with acute myeloid leukemia (AML).

180 therapy regimens for acute myeloid leukemia (AML).

181 approximately 12% of acute myeloid leukemia (AML).

182 c leukemia (ALL) and acute myeloid leukemia (AML).

183 is CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant.

184 ting primary murine acute myeloid leukemias (AMLs) generated by retroviral insertional mutagenesis in

185 n stromal cells from a high frequency of MDS/AML patients, a finding that together with our results h

186 ays, leading to myelomonocytic and monocytic AML cell differentiation.

187 als that GLI3 expression is silenced in most AML patient samples, and the GLI3 locus is abnormally me

188 Mouse AML and BC-CML stem cells were MHCI+ without IFN-gamma s

189 d significantly prolonged survival in murine AML xenografts.

190 med a secondary screen in a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein

191 r patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit.

192 -ITD NK-AML in contrast to wild-type FLT3 NK-AML.

193 activity in G0 arrested primary FLT3-ITD NK-AML in contrast to wild-type FLT3 NK-AML.

194 In these patients with nonfavorable AML according to European LeukemiaNet, disease-free surv

195 Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classifi

196 One feature of cytogenetically normal AML is alterations to the DNA methylome.

197 ions occur in less than one tenth of de novo AML cases.

198 yping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies

199 , 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS.

200 e CSF3R mutations, which are rare in de novo AML, are so prevalent in SCN/AML.

201 sed the clonogenic potential of relapsed NRI AMLs in vitro and prevented the development of relapsed

202 ous relapse with NRAS(V12)-independent (NRI) AMLs providing an opportunity to identify mechanisms tha

203 fer, increase AML apoptosis, and improve NSG AML mouse survival.

204 itors and reflect the de novo acquisition of AML-specific enhancers.

205 s as playing a role in nearly all aspects of AML disease development, including cellular proliferatio

206 rotein expression induced chemoresistance of AML cell lines and primary cells in vitro and in vivo.

207 and overall survival in multiple cohorts of AML patients receiving treatment with the cytidine nucle

208 island hypermethylation is a consequence of AML progression.

209 Here, we report the first description of AML programming bone marrow adipocytes to generate a pro

210 calized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical acti

211 estoration of GLI3R suppresses the growth of AML.

212 f recurrently mutated genes in CR marrows of AML patients at levels as low as 0.002% variant allele f

213 epletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activit

214 In a mouse model of AML, the loss of Cdc42 abrogates MLL-AF9-induced AML dev

215 Using in vivo and in vitro models of AML, we show that bone marrow adipocytes from the tumor

216 tion, and induced cytotoxicity in a panel of AML cell lines.

217 ) and establish ZEB2 as a novel regulator of AML proliferation and differentiation.

218 This increased risk of AML and CML after RAI treatment was seen even in low-ris

219 TP53 mutations are identified in a subset of AML patients and confer an inferior overall survival.

220 te therapeutics in this aggressive subset of AML.

221 ecific enhancers predict overall survival of AML patients.

222 irings hold great promise for CAR therapy of AML.

223 the doors for a more efficient treatment of AML in the clinic.

224 fide therapeutic target for the treatment of AML.

225 verall, our findings illustrate the value of AML-iPSCs for investigating the mechanistic basis and cl

226 tment in adult patients with advanced MDS or AML.

227 ltrombopag, 22 (47%) patients to placebo) or AML (48 [49%] patients to eltrombopag, 25 [53%] patients

228 nistration of SPHK1 inhibitors to orthotopic AML patient-derived xenografts reduced tumor burden and

229 One outlier AML responded and exhibited intrinsic drug resistance at

230 RAS, KRAS and WT1 were frequent in pediatric AML.

231 ted therapies for the treatment of pediatric AML.

232 sought to comprehensively profile pediatric AML microRNA (miRNA) samples to identify dysregulated ge

233 uble-mutant models developed high-penetrance AML, although latency was significantly longer with Npm1

234 ptional memory from cells of origin predicts AML patient survival and allows beta-catenin-independent

235 factor (MIF) was highly expressed by primary AML, and that IL8 was increased in AML/BM-MSC cocultures

236 The role and targeting of SPHK1 in primary AML, however, has not been previously investigated.

237 ished AML, miR-99 inhibition induced primary AML patient blasts to undergo differentiation.

238 endent cell death in AML cell lines, primary AML patient blasts, and isolated AML patient leukemic pr

239 ents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture cond

240 xenograft models and mouse models of primary AML.

241 the AML cell lines MOLM-4, THP-1 or primary AML cells with donor peripheral blood mononuclear cells

242 tologic responses in patients for whom prior AML therapy had failed.

243 mpensatory signaling mechanism that promotes AML cell survival during FLT3 inhibition.

244 vironment plays a critical role in promoting AML cell survival.

245 w mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apo

246 rapy in patients with relapsed or refractory AML and have informed subsequent phase 2 clinical develo

247 Among patients with relapsed or refractory AML, overall response rate was 40.3%, with a median resp

248 research yield important insights regarding AML genetic, epigenetic, evolutional, and clinical diver

249 ro and prevented the development of relapsed AML in vivo.

250 Pre-therapy plasma of refractory/relapsed AML patients contains elevated levels of immunosuppressi

251 3(-/-) MEPs are transformed to self-renewing AML-initiating cells and are capable of inducing AML in

252 applications against chemotherapy-resistant AML.Significance: These findings reveal a mitochondrial

253 In mouse models of retroviral AML transplantation, as well as in retrospective analyse

254 identify this miRNA as a marker of high-risk AML.

255 et (ELN) 2010 intermediate I prognostic risk AML (EFS, 26% +/- 4 vs 40% +/- 5 at 4 years; Cox P = .00

256 rong disease accelerators in a RUNX1-RUNX1T1 AML mouse model, suggesting that H3K27me2/3 has an impor

257 rare in de novo AML, are so prevalent in SCN/AML.

258 s, the truncated G-CSFRs associated with SCN/AML may protect myeloid precursor cells from apoptosis i

259 , low-risk MDS, high-risk MDS, and secondary AML.

260 dities with interventions alongside specific AML therapy might improve survival.

261 receptor 2 antagonism triggered synergistic AML cell death.

262 Using intravital microscopy, we found that AML progression leads to differential remodeling of vasc

263 In the stroma-based conditions, the AML patient cells exhibited significantly reduced sensit

264 Coculture of the AML cell lines MOLM-4, THP-1 or primary AML cells with d

265 omes isolated from pre-therapy plasma of the AML patients receiving adoptive NK-92 cell therapy block

266 tatistic and AUC estimates compared with the AML comorbidity index for prediction of 1-year mortality

267 Thus, AML cells have increased cytidine nucleoside kinase acti

268 143) binds strongly to AML cell lines and to AML primary cells inhibiting their chemotaxis in respons

269 leukemia (AML), and progression from SCN to AML is accompanied by mutations in CSF3R encoding the gr

270 gG1 antibody (PF-06747143) binds strongly to AML cell lines and to AML primary cells inhibiting their

271 could potentially be used in humans to treat AML.

272 This signature identified two AML subsets with different genetic complexity and differ

273 er mitochondria than controls from untreated AML animals.

274 Here, we used AML cells that already had low PU.1 levels and further i

275 ies appears to be rather frequent in various AML entities, bearing, presumably, a greater impact than

276 ells (HSPC-NK cells) in in vitro and in vivo AML models.

277 x 10(9) platelets per L) and disease (MDS vs AML).

278 profile in cultured human AML compared with AML cultured with BM-MSCs and found that macrophage migr

279 Of the 43249 patients with AML (mean [SD] age, 59.5 [16.6] years; 23939 men and 193

280 and event-free survival among patients with AML and a FLT3 mutation.

281 We have demonstrated that patients with AML exhibit increased presence of MDSCs in their periphe

282 chemotherapy option in younger patients with AML in first remission.

283 nt option for thrombocytopenic patients with AML or MDS who are ineligible for other treatment and wh

284 for potential myeloablation in patients with AML treated with CD123-redirected CAR T cells and mandat

285 valuated their impact in 1,328 patients with AML who underwent HCT from 9/10 or 10/10 HLA-matched unr

286 retrospective cohort study of patients with AML who were >/= 66 years of age at diagnosis and diagno

287 y improves survival in elderly patients with AML without increasing toxicity.

288 influenced 1-year survival of patients with AML, and comorbidities are best captured by an augmented

289 etrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was invers

290 er PU.1lo mutant mice or human patients with AML-inhibited cell growth and clonogenicity and induced

291 presence in disease relapse in patients with AML.

292 ration of malignant cells from patients with AML.

293 rates and survival in younger patients with AML.

294 an increase in survival among patients with AML.

295 y profile as a single agent in patients with AML.

296 27M) and H3(K27I) mutations in patients with AML.

297 g growth of leukemic blasts in patients with AML.

298 d a lower IFN response compared with FLT3-WT AML samples.

299 ) AML compared with FLT3 wild-type (FLT3-WT) AML and is critical for the growth of FLT3-ITD(+) AML ce

300 Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for