ライフサイエンスコーパス: AML

1 AML is a genetically heterogeneous disease and understan

2 AML measurable residual disease (MRD) status before allo

3 AML originates from a dominant mutation, then acquires c

4 AML with TET2 mutations was characterized by a particula

5 althy donors killed CBFB-MYH11+ HLA-B*40:01+ AML cell lines and primary human AML samples in vitro.

6 Then, we tested 139 AML cases and 14 different AML cell lines by assessing m

7 to RUNX1 rather than to AML1-ETO in t(8;21) AML cells.

8 following induction chemotherapy (IC) in 97 AML patients.

9 cells for the treatment of NPM1c(+)HLA-A2(+) AML may limit on-target-off-tumour toxicity and tumour r

10 f eradicating NPM1-mutated clones to achieve AML cure and the impact of preleukemic clonal hematopoie

11 In older adults, AML confers an adverse outcome(1,2).

12 ferroptosis that by itself minimally affects AML cells.

13 NR4As interact with an AML-selective SE cluster that governs MYC transcription

14 fferences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be

15 t repressing SE-dependent MYC expression and AML growth in mouse xenografts.

16 nding of key regulators of hematopoiesis and AML pathogenesis.

17 ly narrow cancer spectrum, primarily MDS and AML.

18 activity is required for PLP production and AML cell proliferation, and pharmacological blockade of

19 rlying mechanisms could help to improve anti-AML immunity.

20 vated dendritic cells, evoking a potent anti-AML response.

21 Biomaterial-based AML vaccination can induce potent immune responses, depl

22 b-study; 224 (56.7%) were enrolled on a Beat AML sub-study.

23 in 7 d and were centrally assigned to a Beat AML sub-study; 224 (56.7%) were enrolled on a Beat AML s

24 Analysis of the TARGET and BEAT AML databases identifies a correlation between CD82 expr

25 e prospectively enrolled on the ongoing Beat AML trial (ClinicalTrials.gov NCT03013998 ), which aims

26 antly different between patients on the Beat AML sub-studies and those receiving SOC (induction with

27 Given the complex interactions between AML cells and the many components of their environment,

28 Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therap

29 omycin selectively eliminated CD34(+)CD38(-) AML cells.

30 nd treatment, as well as for targeting CD83+ AML, warrants clinical investigation.

31 Furthermore, treatment of Cdx2 AML with azacitidine decreases leukemic burden.

32 e developed an unbiased approach to classify AML patients into low versus high WBP5 expressers and to

33 bitors, these modalities were unable to cure AML or significantly extend the lives of patients with a

34 che-mediated pro-survival signaling, dampens AML blast regeneration, and strongly synergizes with che

35 can induce potent immune responses, deplete AML cells and prevent disease relapse.

36 -of-care cytoreductive chemotherapy depletes AML cells to induce remission, but is infrequently curat

37 tated AML cell line THP1 and patient-derived AML cells, we tested a new echinomycin formulation with

38 1-overexpressed Hopx(-/-) BM cells developed AML with more aggressive phenotypes compared with those

39 that individuals at high risk of developing AML might benefit from targeted epigenetic therapy in a

40 sease subgroups were: 89% in newly diagnosed AML (62 of 70 patients; 79-94), 80% in untreated seconda

41 and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refra

42 MDSCs has been described in newly diagnosed AML patients, and deciphering the underlying mechanisms

43 d 168 patients; 70 (42%) had newly diagnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had t

44 (95% CI 9.0-not reached) in newly diagnosed AML, 5.1 months (95% CI 0.9-not reached) in untreated se

45 tients (aged >60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary

46 ndependence in patients with newly diagnosed AML.

47 en, we tested 139 AML cases and 14 different AML cell lines by assessing microRNA (miRNA) expression,

48 Across diverse AML cell-line and patient-derived xenograft models, we f

49 al stress of infectious challenges may drive AML progression in molecularly defined subsets and ident

50 ational frequency cancers like fusion-driven AML.

51 between NPM1 and other mutations in driving AML with different outcomes is presented.

52 reatment of FLT3 internal tandem duplication AML cells with quizartinib, a selective FLT3 inhibitor,

53 g this interaction in NUP98-PHF23 expressing AML cells leads to cell death through necrotic and late

54 in CTCF occupancy that targets key genes for AML development and impacts gene expression.

55 itors as a new rational treatment option for AML patients with NUP98-fusions.

56 , may provide a novel therapeutic option for AML.

57 hibitor, as a potential targeted therapy for AML patients with an MLL rearrangement and an FLT3-ITD.

58 to hematologic malignancies (RUNX1-FPD, FPD/AML, FPDMM); ~44% of affected individuals progress to AM

59 stant AML cell lines and primary blasts from AML patients, while showing no cytotoxicity against norm

60 tigen, cell lysates or antigens sourced from AML cells recruited in vivo) induces local immune-cell i

61 Genomically heterogeneous AML has a tendency to evolve, particularly under selecti

62 DK6 was highly expressed in murine and human AML samples.

63 le activity and inhibited apoptosis in human AML cell lines and primary cells.

64 es constitutes "LSC-specific" genes in human AML.

65 LA-B*40:01+ AML cell lines and primary human AML samples in vitro.

66 In primary human AML, exposure of fresh blast cells to daunorubicin activ

67 cally and transcriptionally similar to human AML cells, but only in mice producing IL-3, GM-CSF, and

68 An immunosuppressive AML microenvironment in the bone marrow and the paucity

69 r a selective and critical role of ALKBH5 in AML that might act as a therapeutic target of specific t

70 ession of genes with changed CTCF binding in AML, as well as loss of RUNX1 binding at RUNX1/CTCF-bind

71 d been in place for almost half a century in AML.

72 decitabine-induced transcriptome changes in AML cell lines with or without a deletion of chromosomes

73 n combination with intensive chemotherapy in AML is unknown.

74 D2 and CDC20 expression, and promoted CIN in AML cells.

75 rease subsequent infectious complications in AML patients.Baseline microbiome diversity is a strong i

76 resent current evidence on immune defects in AML, discuss the challenges with selective targeting of

77 Recently age-specific differences in AML have been identified, highlighting the need for tail

78 ly, ALKBH5 exerts tumor-promoting effects in AML by post-transcriptional regulation of its critical t

79 the new treatment challenges encountered in AML management, with the goal of providing practical gui

80 ate both genetic and phenotypic evolution in AML.

81 MAD2 and CDC20 were aberrantly expressed in AML patients.

82 y alters the expression of adjacent genes in AML.

83 the intriguing clinical activity of HMAs in AML/MDS patients with chromosome 7 deletions and other m

84 We next examined the role of Hopx in AML by using the MN1 overexpression murine leukemia mode

85 us explaining the genomic hypomethylation in AML cells.

86 egarding the biological function of IL2RA in AML is available.

87 surmise that the future of immunotherapy in AML lies in the rational combination of complementary im

88 fferentiation mediator downstream of KLF4 in AML cells.

89 Inhibiting MTCH2 in AML cells increased nuclear pyruvate and pyruvate dehydr

90 d so lacks the region of sequence mutated in AML).

91 The most frequent DNMT3A mutation in AML patients (R882H) encodes a dominant-negative protein

92 findings show that ROS generated by NOX2 in AML cells promotes glycolysis by activating PFKFB3 and s

93 on and its impact on the survival outcome in AML patients remains largely understudied.

94 in lipid catabolism that supports OxPHOS in AML cells.

95 erefore, targeting protein palmitoylation in AML blasts could block MDSC accumulation to improve immu

96 ate that targeting protein palmitoylation in AML could interfere with the leukemogenic potential and

97 roved quality of life without a reduction in AML disease burden.

98 the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression

99 key regulators of chemotherapy resistance in AML.

100 ET2 and EZH2 play a tumor-inhibiting role in AML that affects CIN via MAD2 and CDC20.

101 ime that IL2RA plays key biological roles in AML and underscore its value as a potential therapeutic

102 rapid occurrence of therapeutic selection in AML.

103 for attenuating chemoresistance signaling in AML.

104 emical insights into a therapeutic target in AML will enable the clinical translation of these findin

105 gest PFKFB3 as a novel therapeutic target in AML.

106 dentify potential immune-mediated targets in AML.

107 f multiple different malignancies, including AML.

108 Studies including AMLs with macroscopic fat and studies with insufficient

109 Retroviral overexpression of Cdx2 induces AML in mice, however the developmental stage at which CD

110 t enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products par

111 l for shorter-term mortality after intensive AML chemotherapy.

112 , patients with MDS before transforming into AML (MDS-T), and patients with AML evolving from MDS (MD

113 In patient-derived monosomal karyotype AML murine xenografts, decitabine treatment resulted in

114 leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem ce

115 Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by genetic

116 Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcr

117 Acute myeloid leukaemia (AML) is a malignancy of haematopoietic origin that has l

118 nosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive c

119 5% of patients with acute myeloid leukaemia (AML).

120 me in patients with Acute Myeloid Leukaemia (AML).

121 the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase

122 Using acute myelogenous leukemia (AML) patient-derived xenograft (PDX) models of acquired

123 recurrently found in acute myeloid leukemia (AML) and are associated with poor prognosis.

124 eport a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49

125 n aggressive form of acute myeloid leukemia (AML) and poor survival rate.

126 r differentiation in acute myeloid leukemia (AML) and small cell lung cancer (SCLC) cell lines, and a

127 enzymes required for acute myeloid leukemia (AML) cell growth.

128 Primary acute myeloid leukemia (AML) cells harvested from patients with NPM1mutFLT3mut A

129 nce of NOD2 in human acute myeloid leukemia (AML) cells, demonstrating that IFN-gamma treatment upreg

130 ry for the growth of acute myeloid leukemia (AML) cells, we identified the mitochondrial outer membra

131 d genetic studies in acute myeloid leukemia (AML) cells.

132 itable for intensive acute myeloid leukemia (AML) chemotherapy.

133 hat are required for acute myeloid leukemia (AML) development.

134 We show that human acute myeloid leukemia (AML) expresses CD83 and that myeloid leukemia cell lines

135 Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs)

136 lapsed or refractory acute myeloid leukemia (AML) has presented challenges for hematologists for deca

137 garding treatment of acute myeloid leukemia (AML) include achieving complete remission (CR) by clinic

138 Acute myeloid leukemia (AML) is a cancer derived from the myeloid lineage of blo

139 Acute myeloid leukemia (AML) is a deadly hematologic malignancy with poor progno

140 Acute myeloid leukemia (AML) is a systemic, heterogeneous hematologic malignancy

141 Acute myeloid leukemia (AML) is an attractive system for investigating the effec

142 Acute myeloid leukemia (AML) is characterised by a series of genetic and epigene

143 hallenge in treating acute myeloid leukemia (AML) is chemotherapy refractory disease.

144 , but progression to acute myeloid leukemia (AML) is rare.

145 tic reprogramming in Acute Myeloid Leukemia (AML) leads to the aberrant activation of super enhancer

146 Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammato

147 the highly prevalent acute myeloid leukemia (AML) mutation, Arg882His, in DNMT3A disrupts its coopera

148 lls derived from six acute myeloid leukemia (AML) patients and treated with the nucleoside analog DAC

149 in a pilot study in acute myeloid leukemia (AML) patients who entered complete remission.

150 nal histories of 123 acute myeloid leukemia (AML) patients.

151 Acute myeloid leukemia (AML) represents the most common acute leukemia among adu

152 evant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhan

153 nce in patients with acute myeloid leukemia (AML) treated with the isocitrate dehydrogenase 2 (IDH2)

154 ultra-deep sequenced acute myeloid leukemia (AML) tumor and identify known cancer genes and additiona

155 re for patients with acute myeloid leukemia (AML) who undergo allogeneic stem cell transplantation (a

156 Acute myeloid leukemia (AML) with inv(3)/t(3;3)(q21q26) is a distinct World Heal

157 Acute myeloid leukemia (AML) with mixed lineage leukemia 1 (MLL1) gene rearrange

158 h CD33 expression in acute myeloid leukemia (AML) with mutated NPM1 provides a rationale for the eval

159 id transformation to acute myeloid leukemia (AML)(5), resistance to conventional therapies(6-8) and d

160 However, in acute myeloid leukemia (AML), ALKBH5 was reported to be frequently deleted, impl

161 kemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia st

162 Alzheimer's disease, acute myeloid leukemia (AML), and influenza.

163 c Syndrome (MDS) and Acute Myeloid Leukemia (AML), and the most common mutation is a missense substit

164 sent our results for acute myeloid leukemia (AML), breast cancer and prostate cancer.

165 rylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells.

166 with newly diagnosed acute myeloid leukemia (AML), immediate treatment start is recommended due to th

167 H11 are prevalent in acute myeloid leukemia (AML), often necessary for leukemogenesis, persistent thr

168 an emerging role in acute myeloid leukemia (AML), with promising response rates in combination with

169 lderly patients with acute myeloid leukemia (AML).

170 ne aggressiveness of acute myeloid leukemia (AML).

171 osome aberrations in acute myeloid leukemia (AML).

172 a poor prognosis in acute myeloid leukemia (AML).

173 promotes relapse in acute myeloid leukemia (AML).

174 n the development of acute myeloid leukemia (AML).

175 n of its promoter in acute myeloid leukemia (AML).

176 use model of inv(16) acute myeloid leukemia (AML).

177 innate resistance in acute myeloid leukemia (AML).

178 IDH1-mutant (mIDH1) acute myeloid leukemia (AML).

179 ently deregulated in acute myeloid leukemia (AML).

180 essed and mutated in acute myeloid leukemia (AML).

181 mes in patients with acute myeloid leukemia (AML).

182 Secondary acute myeloid leukemias (AMLs) evolving from an antecedent myeloproliferative neo

183 In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determi

184 and patients with AML evolving from MDS (MDS-AML).

185 0 years was the biggest risk factor, and MDS/AML usually manifested with marrow hypoplasia and monoso

186 In one-half of the cases, MDS/AML patients showed a recurrent peripheral blood pattern

187 and 39%, respectively, and two-thirds of MDS/AML patients died of pulmonary fibrosis and/or hepatopul

188 7RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPR

189 PNH patients go on to develop secondary MDS/AML by 10 years of follow-up.

190 er adult short telomere patients without MDS/AML also had evidence of clonal hematopoiesis of indeter

191 therapeutic strategy for CEBPA/CSF3R mutant AML.

192 were noted in NPM1-, IDH2-, and SRSF2-mutant AML.

193 n these patients with RUNX1 germline-mutated AML.

194 ave been recurrently detected in IDH-mutated AML samples.

195 xpression to the development of NPM1-mutated AML is also highlighted.

196 and clinical issues related to NPM1-mutated AML.

197 on and consolidation therapy in NPM1-mutated AML.

198 Using TP53-mutated AML cell line THP1 and patient-derived AML cells, we tes

199 stablished a xenograft model of TP53-mutated AML.

200 unt recovery) was 72%; it was 97% in de novo AML and was 43% in secondary AML.

201 and molecular features distinct from de novo AML.

202 ce of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase 3 AMLSG 09-09 trial

203 harvested from patients with NPM1mutFLT3mut AML showed significantly better responses to combined me

204 Furthermore, 40% of AML cell lines showed a combined loss of the expression

205 s have enabled highly sensitive detection of AML-associated mutations and translocations, determinati

206 subsequently promoted the differentiation of AML cells.

207 le for CBFA2T3 in myeloid differentiation of AML has not been reported.

208 hosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a sig

209 In a murine model of AML, dual treatment with MTP-PE and IFN-gamma led to a s

210 Models of AML MRD also showed benefit for MAC over RIC for those w

211 Here, in mouse models of AML, we show that a macroporous-biomaterial vaccine that

212 n underscores the immunoresponsive nature of AML, creating the basis for further exploiting immunothe

213 In this study, we compared outcomes of AML patients >60 years of age undergoing allogenic hemat

214 l clonal diversity and evolution patterns of AML, and highlight their clinical relevance in the era o

215 ntributes to the chemoresistant phenotype of AML.

216 hat ROS production promotes proliferation of AML cells.

217 The stratification of AML patients, based on miR-15/16 expression, can lead to

218 In this subtype of AML, the translocation of a GATA2 enhancer (3q21) to MEC

219 A nuclear receptors are tumor suppressors of AML that function in part through transcriptional repres

220 ween CD82 expression and overall survival of AML patients.

221 s the challenges with selective targeting of AML cells, and summarize the clinical results and immuno

222 , the combination of MTP-PE and IFN-gamma on AML blasts generated an inflammatory cytokine profile an

223 les, we investigated the effects of IL2RA on AML cell proliferation and apoptosis, and on pertinent s

224 ts showed that 30% of RUNX1 mutations in our AML cohort are germline.

225 redominantly affecting infant and paediatric AML and ALL patients.

226 f 80 apoptotic-inducing agents in paediatric AML pre-clinical models.

227 ons (ITDs) have poor outcomes, in particular AML with a high (>=0.5) mutant/wild-type allelic ratio (

228 diagnostic performance of MRI for lipid-poor AMLs in patients with renal masses.

229 1), 83 adult patients with FLT3-ITD-positive AML in complete hematologic remission after HCT were ran

230 broad range of human cell lines and primary AML cells from patients.

231 hole metabolome analysis of 20 human primary AML showed that blasts generating high levels of ROS hav

232 ceramide were also down-regulated in primary AML cells.

233 tently expressed at higher levels in primary AML patient samples than in CD34+ progenitors, monocytes

234 combination has been validated using primary AML patient samples and xenograft mouse models.

235 tion of the mechanism by which CD82 promotes AML survival in response to chemotherapy identified a cr

236 poptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xenograft mice.

237 lectively eliminating LSCs in MLL-rearranged AML.

238 poiesis in a murine model of MLL1-rearranged AML, associated with accelerated leukemogenesis.

239 kemia suppressor function in MLL1-rearranged AML.

240 w progenitors from mice with MLL1-rearranged AML.

241 kemia stem cell expansion in MLL1-rearranged AML.

242 sified as a single entity of 3q26-rearranged AMLs.

243 ch the MAIT TCR can differentially recognize AMLs, thereby providing insight into MAIT cell antigen s

244 s; 42-76), and 62% in relapsed or refractory AML (34 of 55 patients; 49-74).

245 ly defined subsets of relapsed or refractory AML.

246 cytic leukaemia); and relapsed or refractory AML.

247 I 6.6-not reached) in relapsed or refractory AML.

248 visit the approach to relapsed or refractory AML.

249 AML, and 55 (33%) had relapsed or refractory AML.

250 topoiesis (CH) that may not reflect residual AML.

251 ecrosis in several mutant and FLT3-resistant AML cell lines and primary blasts from AML patients, whi

252 utcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status.

253 Using the Leucegene RUNX1 AML patient group, we sought to investigate the proporti

254 lliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry.

255 oiesis persistence in predisposing to second AML.

256 yelodysplastic syndromes (MDS) and secondary AML (sAML).

257 MDS and secondary AML cells harbor mutations in many of the same genes and

258 quency of mutated genes in MDS and secondary AML indicate that the order of mutation acquisition is n

259 igible for intensive chemotherapy; secondary AML (progressed after myelodysplastic syndrome or chroni

260 97% in de novo AML and was 43% in secondary AML.

261 oproliferative neoplasm (post-MPN) secondary AML (sAML) cells demonstrated accessible and active chro

262 ne advances in the study of MDS to secondary AML progression, with a focus on the genetics of progres

263 fication, and monitoring of MDS to secondary AML progression.

264 5 patients; 55-93), 61% in treated secondary AML (17 of 28 patients; 42-76), and 62% in relapsed or r

265 not reached) in previously treated secondary AML, and 16.8 months (95% CI 6.6-not reached) in relapse

266 econdary AML, 28 (17%) had treated secondary AML, and 55 (33%) had relapsed or refractory AML.

267 patients; 79-94), 80% in untreated secondary AML (12 of 15 patients; 55-93), 61% in treated secondary

268 agnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had treated secondary AML, and 55 (33%) ha

269 % CI 0.9-not reached) in untreated secondary AML, not reached (95% CI 2.5-not reached) in previously

270 myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulat

271 of miR-15a/-15b/-16 significantly stratified AML patients in two prognostic classes.

272 r aberrations are routinely used to stratify AML patients into prognostic subgroups when receiving st

273 unotherapy approaches to specifically target AML cells (antibodies, cellular therapies) or more broad

274 f of principle for immunologically targeting AML-initiating fusions and demonstrate that targeting ne

275 We conclude that AML displays an aberrant increase in CTCF occupancy that

276 t/mTOR pathway played a critical role in the AML-EV-induced phenotypical and functional transition of

277 Splenic uptake was higher in the AML/MDS group than in the lymphoma group (P <= 0.05) or

278 Moreover, the 3q26 translocations in these AML patients often involve superenhancers of genes activ

279 uation of gemtuzumab ozogamicin (GO) in this AML entity.

280 se and contributes to leukemogenesis in this AML subtype.

281 that H3K9 acetylation changes are linked to AML-relevant signaling pathways like EGF/EGFR and Wnt/He

282 gulatory influence of TEs and their links to AML pathogenesis remain unexplored.

283 M); ~44% of affected individuals progress to AML or myelodysplastic syndromes.

284 es are frequently insensitive to traditional AML chemotherapeutic agents.

285 Our data suggest a novel approach to treat AML with TP53 mutations.

286 Treating AML cells with an EZH2 inhibitor partially restored the

287 riched in TP53-mutated versus TP53-wild-type AML.

288 and CEBPA germline mutations, with variable AML disease onset at 59 and 27 years, respectively.

289 e-drug or vehicle control treatment, whereas AML cells with wild-type NPM1, MLL, and FLT3 were not af

290 MSC niche, and a molecular mechanism whereby AML impairs normal hematopoiesis by remodeling the mesen

291 enriched for gain in promoter regions, while AML in general was enriched for changes at enhancers.

292 nalyzed clinical features of 172 adults with AML and recurrent 11q23/KMT2A rearrangements, 141 of who

293 ix endogenous retrovirus (ERV) families with AML-associated enhancer chromatin signatures that are en

294 Untreated patients with AML >= 60 years were prospectively enrolled on the ongoi

295 OX2 oxidase, occurs in >60% of patients with AML and that ROS production promotes proliferation of AM

296 In summary, older patients with AML benefited from a reduced-intensity conditioning regi

297 sforming into AML (MDS-T), and patients with AML evolving from MDS (MDS-AML).

298 lloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and im

299 gnosis and survival outcome in patients with AML.

300 afe and tolerable in fit older patients with AML.