ライフサイエンスコーパス: T-ALL

1 T-ALL is an heterogeneous disease, which presents intrin

2 T-ALL NOTCH1 mutations result in ligand-independent and

3 tric (6 of 160) and 5.5% of adult (9 of 163) T-ALL patient samples.

4 Using integrated genomic analysis of 264 T-ALL cases, we identified 106 putative driver genes, ha

5 d most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking establish

6 tations were identified in PF-382 and DU.528 T-ALL cell lines in addition to 3.7% of pediatric (6 of

7 A total of 111 patients with T-ALL/LBL (68% T-ALL; 32% T-LBL) with adequate immunophenotype data wer

8 Our data identify a T-ALL niche and suggest targeting CXCL12/CXCR4 signaling

9 ene was first implicated as an oncogene in a T-ALL mouse model expressing myristoylated (Myr) Akt2.

10 suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts.

11 h lesions in many other genes to cause acute T-ALL.

12 notype of immunophenotypically defined adult T-ALL is similar to the pediatric equivalent, with high

13 ing may be therapeutically efficient against T-ALL relapse, we focused on a known Notch1-induced T-AL

14 enotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates of intrinsic treatment

15 ntly greater efficacy against T-lineage ALL (T-ALL) than B-cell-precursor ALL (BCP-ALL) xenografts.

16 subtypes had lower MTXPG levels (T cell ALL [T-ALL] and B cell ALL [B-ALL] with the TCF3-PBX1 or ETV6

17 4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent a

18 Yet, although T-ALL infiltration and progression are independent of th

19 cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AM

20 ression of target antigens between CARTs and T-ALL blasts leads to CART fratricide.

21 Cell models of AML, CML, and T-ALL were potently affected by KDM1A inhibition, and ce

22 rapeutic use of PARP inhibitors in DLBCL and T-ALL.

23 dly different oncogene activations in EL and T-ALL: Notch1 and Ikaros were most common in T-ALL, wher

24 tant JAK3 to drive T-cell transformation and T-ALL development.

25 at occur within 3 years of diagnosis and any T-ALL relapses are particularly difficult to salvage.

26 les for current treatment protocols for both T-ALL and T-lymphoblastic lymphoma.

27 In addition, using different CD127+ T-ALL/T-LBL xenograft models, we also reveal that residu

28 r Moloney-murine leukemia 1 (PIM1) in CD127+ T-ALL/T-LBL, thereby rendering these tumor cells sensiti

29 e leukemia survival in a PDX model of CD127+ T-ALL.

30 PIM1 and suggests that IL7-responsive CD127+ T-ALL and T-LBL patients could benefit from PIM inhibiti

31 properties in xenograft (PDX) models of CD3+ T-ALL, resulting in prolonged host survival.

32 d not previously been described in childhood T-ALL (for example, CCND3, CTCF, MYB, SMARCA4, ZFP36L2 a

33 In childhood T-ALL, the N/F/R/P mutation profile is an independent pr

34 he frontline Children's Oncology Group (COG) T-ALL clinical trial AALL1231, we demonstrated that one-

35 In all tested conditions, T-ALL reached an incidence of 80%, demonstrating that th

36 CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained a

37 ted ALL, PTPN2 mutations in TLX1 deregulated T-ALL, and PIK3R1/PTEN mutations in TAL1 deregulated ALL

38 ar models of AML and primary patient-derived T-ALL cells.

39 graftment and progression of patient-derived T-ALL xenografts.

40 ras(G12D) mice transduced with Myc developed T-ALLs that were GSI-insensitive and lacked Notch1 mutat

41 ildren and young adults with newly diagnosed T-ALL without increased toxicity.

42 Patients with newly diagnosed T-ALL/LBL who received frontline chemotherapy between th

43 erexpression of Dlx5 was sufficient to drive T-ALL in mice by directly activating Akt and Notch signa

44 e capacity to cooperate with Notch1 to drive T-ALL.

45 tumor-associated DCs supply signals driving T-ALL growth, and implicate tumor-associated DCs and the

46 However, in TAL1-expressing T-ALL cells, the leukemia-prone TAL1 promoter-IV specifi

47 P4L might represent a promising approach for T-ALL treatment.

48 aling as a powerful therapeutic approach for T-ALL.

49 malignancies, they are not yet available for T-ALL.

50 d myeloid cells provide signals critical for T-ALL growth in multiple organs in vivo and implicate tu

51 nd no effective targeted immunotherapies for T-ALL exist.

52 We found no influence for T-ALL in the specific combination of the genotypic mutat

53 el and less-toxic therapeutic strategies for T-ALL/T-LBL patients has largely focused on the identifi

54 Improving therapies for T-ALL requires the development of strategies to target p

55 develop personalized epigenetic therapy for T-ALL patients.

56 xploited as an additional target therapy for T-ALL.

57 KRAS(G12D) T-ALLs do not show constitutive GTP loading of Ras.

58 opoiesis using a T-ALL mouse model and human T-ALL xenografts.

59 hat Ras-induced mouse T-ALL as well as human T-ALL carrying mutations in the RAS/MAPK pathway display

60 nt in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interv

61 s well-known target, Etv4 Importantly, human T-ALL also relies on ETV4 expression for maintaining its

62 wth in vivo and that RUNX silencing in human T-ALL cells triggers apoptosis.

63 e it is induced by the TAL1 complex in human T-ALL cells.

64 1, one of the most common mutations in human T-ALL, suggesting Idh1 mutations may have the capacity t

65 o RUNX proteins, impairs the growth of human T-ALL cell lines and primary patient samples.

66 in silico gene expression analysis of human T-ALL samples we observed a significant correlation betw

67 olesterol synthesis pathway in primary human T-ALL specimens.

68 Similarly, human T-ALL cell lines with activated NOTCH and AKT and elevat

69 cell leukemia homeobox 1/3-transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models.

70 rimary tumors extend recent work using human T-ALL cell lines and xenografts and suggest that the Not

71 f ZEB2 and demonstrated that mouse and human T-ALLs with increased ZEB2 levels critically depend on K

72 FLT3 mutations were associated with immature T-ALL, JAK3/STAT5B mutations in HOXA1 deregulated ALL, P

73 In T-ALL cell lines overexpression of RASGRP1 increases flu

74 In T-ALL cell lines, pharmacological inhibition or short in

75 In T-ALL, deacetylated LMO2 induces expression of TAL1 comp

76 omoter IV interaction for TAL1 activation in T-ALL.

77 iciency led to the induction of apoptosis in T-ALL cells, whereas cell cycle progression remained una

78 er associated long noncoding RNA (ARIEL), in T-ALL pathogenesis.

79 of the newly identified Notch3-Pin1 axis in T-ALL aggressiveness and progression.

80 ctivates the oncogenic regulatory circuit in T-ALL cells.

81 y to tumor suppressive functions of CNOT3 in T-ALL.

82 T-ALL: Notch1 and Ikaros were most common in T-ALL, whereas ETS transcription factors (Erg and Ets1)

83 activity at low micro molar concentration in T-ALL cell lines.

84 Although NOTCH is a known driver in T-ALL, its clinical inhibition has significant limitatio

85 mental pathway that is commonly expressed in T-ALL and has been implicated in leukemia progression; h

86 We demonstrate that ORP4L is expressed in T-ALL but not normal T-cells and its abundance is propor

87 c or MRD >/= 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, th

88 use transcriptional upregulation of IL7RA in T-ALL/T-LBL patient-derived xenograft (PDX) cells, ultim

89 is a strong negative prognostic indicator in T-ALL, the mechanisms of GC resistance remain poorly und

90 ugs that synergize with NOTCH1 inhibition in T-ALL.

91 interactions and TAD boundary insulation in T-ALL.

92 tion is disrupted by the -31CBS inversion in T-ALL cells.

93 he selective pressure for Notch mutations in T-ALL and response and resistance of T-ALL to Notch path

94 e TAL1-induced regulatory circuit and MYC in T-ALL, thereby contributing to T-cell leukemogenesis.

95 t other pathways can substitute for Notch in T-ALL.

96 result, the oncogenic activity of NOTCH1 in T-ALL is strictly dependent on MYC upregulation, which m

97 Our findings uncover a role for NRARP in T-ALL pathogenesis and indicate that Notch inhibition ma

98 ration of the bone marrow commonly occurs in T-ALL and relapsed B-cell acute lymphoblastic leukemia p

99 a key role for Ldb1, a nonproto-oncogene, in T-ALL and support a model in which Lmo2-induced T-ALL re

100 xpression, SCL contributes to oncogenesis in T-ALL.

101 actor RASGRP1 is frequently overexpressed in T-ALL patients.

102 independent of FcgammaR-mediated pathways in T-ALL PDXs.

103 may provide new therapeutic possibilities in T-ALL and may contribute to the development of new metho

104 PLCbeta3 catalyzes IP3 production in T-ALL as opposed to PLCgamma1 in normal T-cells.

105 r involved in the transcriptional program in T-ALL.

106 AL1 regulates the transcriptional program in T-ALL.

107 Aberrant cell growth and proliferation in T-ALL lymphoblasts are sustained by activation of strong

108 lays an oncogenic role as an enhancer RNA in T-ALL.

109 lts indicate that NRARP plays a dual role in T-ALL pathogenesis, regulating both Notch and Wnt pathwa

110 signaling, could have a suppressive role in T-ALL.

111 hat CTCF boundary plays a pathogenic role in T-ALL.

112 or 1 (LEF1) and potentiates Wnt signaling in T-ALL cells with low levels of Notch.

113 the significance of IL-7R/IL-7 signaling in T-ALL pathogenesis and its contribution to disease relap

114 signalling pathway operating specifically in T-ALL cells in which ORP4L mediates G protein-coupled li

115 locus is activated under a superenhancer in T-ALL cells but not in normal T cells.

116 reviously described as a tumor suppressor in T-ALL, is in fact a pro-oncogenic cofactor essential for

117 hog pathway as a novel therapeutic target in T-ALL and demonstrate that hedgehog inhibitors approved

118 eveal RUNX1 as a novel therapeutic target in T-ALL.

119 SP90 pathways as specific vulnerabilities in T-ALL cells with combined JAK3 and SUZ12 mutations.

120 subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characteri

121 stablished that overexpression of RasGRP1 in T-ALLs results in a constitutively high GTP-loading rate

122 es below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic a

123 ated the importance of Ldb1 for Lmo2-induced T-ALL by conditional deletion of Ldb1 in thymocytes in a

124 LL and support a model in which Lmo2-induced T-ALL results from failure to downregulate Ldb1/Lmo2-nuc

125 elapse, we focused on a known Notch1-induced T-ALL model, because a majority of T-ALL patients harbor

126 depletion in a mouse model of Notch3-induced T-ALL, by reducing N3IC expression and signaling, impair

127 al integration sites in gene therapy-induced T-ALL, suggesting that such events occur at preferential

128 Cic inactivation in mice induces T-ALL by a mechanism involving derepression of its well-

129 novel agents, the development of intensified T-ALL-focused protocols has resulted in significant impr

130 but detailed genome-wide sequencing of large T-ALL cohorts has not been carried out.

131 human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the pro

132 ing in T-cell acute lymphoblastic leukaemia (T-ALL), and the involvement of BCL6 in other types of le

133 n highly expressed in acute T-cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas.

134 oproliferative disorder and T cell leukemia (T-ALL) when induced in the bone marrow via Mx1CRE.

135 oods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurre

136 n human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (gamma-secretase inhibitors

137 rapid onset of acute lymphoblastic leukemia (T-ALL) and progressive development of hepatocellular car

138 tion in T-cell acute lymphoblastic leukemia (T-ALL) and RPS15 mutations in chronic lymphocytic leukem

139 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell acute lymphoblastic lymphoma (T-LBL) a

140 lignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significan

141 ractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with ne

142 ture in T cell acute lymphoblastic leukemia (T-ALL) by using primary human leukemia specimens and exa

143 rom 419 T-cell acute lymphoblastic leukemia (T-ALL) cases demonstrated a significant association betw

144 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases.

145 pendent T cell acute lymphoblastic leukemia (T-ALL) cell lines and bound directly to the core Notch t

146 rt that T-cell acute lymphoblastic leukemia (T-ALL) cells are characterized by increased oxidative ph

147 CLs and T cell acute lymphoblastic leukemia (T-ALL) cells exhibit a high sensitivity to poly(ADP-ribo

148 growth, T-cell acute lymphoblastic leukemia (T-ALL) cells require exogenous cells or signals to survi

149 Primary T-cell acute lymphoblastic leukemia (T-ALL) cells require stromal-derived signals to survive.

150 ance in T cell acute lymphoblastic leukemia (T-ALL) cells, and that this could be effectively reverse

151 gram in T-cell acute lymphoblastic leukemia (T-ALL) cells.

152 Jurkat T-cell acute lymphoblastic leukemia (T-ALL) cells.

153 ed with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression.

154 ies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass.

155 ractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted i

156 induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model.

157 taneous T-cell acute lymphoblastic leukemia (T-ALL) in these animals.

158 T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors

159 T-cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy

160 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia that is cause

161 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy resulti

162 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a

163 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumul

164 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for ~20

165 T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that has historically

166 ildhood T-cell acute lymphoblastic leukemia (T-ALL) is mainly based on minimal residual disease (MRD)

167 diatric T-cell acute lymphoblastic leukemia (T-ALL) patients and murine models, in which RasGRP1 T-AL

168 half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the

169 Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocortico

170 bset of T-cell acute lymphoblastic leukemia (T-ALL) patients, and RUNX1 mutations are associated with

171 ated in T-cell acute lymphoblastic leukemia (T-ALL) patients.

172 tic tools in T-acute lymphoblastic leukemia (T-ALL) using T-ALL cell lines and patient-derived sample

173 mmature T-cell acute lymphoblastic leukemia (T-ALL), a heterogenic subgroup of human leukemia charact

174 ts with T cell acute lymphoblastic leukemia (T-ALL), and although resistance to GCs is a strong negat

175 s of T-lineage acute lymphoblastic leukemia (T-ALL), but detailed genome-wide sequencing of large T-A

176 type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic

177 f human T cell acute lymphoblastic leukemia (T-ALL), containing mutations in NOTCH1, TP53, BCL6, BCOR

178 form of T-cell acute lymphoblastic leukemia (T-ALL), designated early T-cell precursor ALL, which is

179 e human T-cell acute lymphoblastic leukemia (T-ALL), in that they predominantly exhibit activating No

180 ment of T cell acute lymphoblastic leukemia (T-ALL), similar to the human disease.

181 role in T cell acute lymphoblastic leukemia (T-ALL), yet the mechanisms underlying its deregulation r

182 bset of T-cell acute lymphoblastic leukemia (T-ALL).

183 rget in T-cell acute lymphoblastic leukemia (T-ALL).

184 cluding T-cell acute lymphoblastic leukemia (T-ALL).

185 gene in T-cell acute lymphoblastic leukemia (T-ALL).

186 ng from T-cell acute lymphoblastic leukemia (T-ALL).

187 TCH1 in T-cell acute lymphoblastic leukemia (T-ALL).

188 MO2) in T-cell acute lymphoblastic leukemia (T-ALL).

189 ociated with T Acute lymphoblastic Leukemia (T-ALL).

190 ML) and T-cell acute lymphoblastic leukemia (T-ALL).

191 eukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal

192 ed with T-cell acute lymphoblastic leukemia, T-ALL, though its contribution to other cancers has not

193 driven T-cell acute lymphoblastic leukemias (T-ALLs) has recently been established.

194 -cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one Rpl22 allele accelerat

195 high-risk T lymphoblastic leukemia/lymphoma (T-ALL/LBL) subgroup.

196 induces T-cell acute lymphoblastic lymphoma (T-ALL), a tumor type known to carry CIC mutations, albei

197 precursors caused T-cell leukemia/lymphomas (T-ALL) and pure red blood cell erythroleukemias (EL).

198 GF1R signaling was necessary for DC-mediated T-ALL survival.

199 ll surface protein mRNAs in an LMO2-mediated T-ALL mouse model and corroborated by protein detection

200 as a critical component of myeloid-mediated T-ALL growth and survival.

201 Finally, we show that Ras-induced mouse T-ALL as well as human T-ALL carrying mutations in the R

202 survival and proliferation of primary mouse T-ALL cells in vitro.

203 c tumor microenvironments in multiple murine T-ALL models and primary patient samples, we discovered

204 xplanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of a

205 y, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are m

206 nce in TAL1-positive (but not TAL1-negative) T-ALL.

207 TAL1 expression in erythroid cells, but not T-ALL cells.

208 ransformed human T-ALL cell lines and NOTCH1 T-ALL mouse models.

209 the hedgehog pathway is activated in 20% of T-ALL samples.

210 of the TAL1 is associated with up to 60% of T-ALL cases and is involved in CTCF-mediated genome orga

211 ling, which is activated in more than 65% of T-ALL patients by activating mutations in the NOTCH1 gen

212 signaling cues in controlling the ability of T-ALL to home, survive, and proliferate, thus offering t

213 bioenergetics, cell death and abrogation of T-ALL engraftment in vivo.

214 This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment

215 pression is an early functional biomarker of T-ALL cells with LIC potential and report that impaired

216 sion profiling allowed the classification of T-ALL into defined molecular subgroups that mostly refle

217 immunophenotype, or pathologic condition of T-ALL.

218 ferences found influenced the development of T-ALL.

219 e in vitro growth and in vivo engraftment of T-ALL cells via diminished LMO2 deacetylation.

220 tch1 signaling, it promotes the expansion of T-ALL cells with lower levels of Notch1 activity.

221 B is required for the survival and growth of T-ALL cells, and forced expression of ARID5B in immature

222 ew, we provide an update on our knowledge of T-ALL pathogenesis, the opportunities for the introducti

223 1-induced T-ALL model, because a majority of T-ALL patients harbor activating mutations in NOTCH1, wh

224 ere protective in a mouse xenograft model of T-ALL.

225 mocytes in an Lmo2 transgenic mouse model of T-ALL.

226 ultiple organs in 2 distinct mouse models of T-ALL and prolongs survival.

227 In mechanistic and translational models of T-ALL, we demonstrate NOTCH1 inhibition in vitro and in

228 ase progression in xenograft mouse models of T-ALL.

229 ing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTC

230 omously, which is required for prevention of T-ALL.

231 H1 signaling and delays the proliferation of T-ALL cells that display high levels of Notch1 signaling

232 ions in T-ALL and response and resistance of T-ALL to Notch pathway inhibitors.

233 In the past decade, systematic screening of T-ALL genomes by high-resolution copy-number arrays and

234 y in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic trans

235 uld have therapeutic efficacy in a subset of T-ALL patients.

236 cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse.

237 genes and pathways, and stage or subtype of T-ALL.

238 f ARIEL inhibits cell growth and survival of T-ALL cells in culture and blocks disease progression in

239 the capacity to directly support survival of T-ALL cells.

240 Although advances in the treatment of T-ALL have lagged behind those of B-cell ALL, it is hope

241 tive therapeutic target for the treatment of T-ALL.

242 n inhibitor combinations in the treatment of T-ALL.

243 d as therapeutic target for the treatment of T-ALL.

244 new therapeutic option for the treatment of T-ALL.

245 s study is important to our understanding of T-ALL.

246 etained during leukemogenesis in a subset of T-ALLs and is reversible with targeted inhibition of the

247 The impact of the myeloid compartment on T-ALL growth is not dependent on suppression of antitumo

248 lin-like growth factor I receptor (Igf1r) on T-ALL cells, with concomitant expression of their ligand

249 e regimens with those of patients with other T-ALL/LBL immunophenotypic subtypes.

250 ransition of preleukemic thymocytes to overt T-ALL.

251 directly support survival of primary patient T-ALL cells in vitro.

252 (siRNNs) targeting Plk1, can enter pediatric T-ALL patient cells without a transfection reagent and i

253 rrelate with inferior outcomes for pediatric T-ALL patients.

254 nded RASGRP1 expression surveys in pediatric T-ALL and generated a RoLoRiG mouse model crossed to Mx1

255 es and overcoming GC resistance in pediatric T-ALL patients.

256 e poorer outcome than do the other pediatric T-ALL patients receiving a high-risk adapted therapy.

257 Dicer1 allele did not significantly perturb T-ALL onset and tumor progression.

258 c interventions, particularly for preventing T-ALL (and B-ALL) relapse.

259 ytarabine in both AML cell lines and primary T-ALL cells.

260 evels are significantly increased in primary T-ALL cells suggesting that NRARP is not sufficient to b

261 Moreover, primary T-ALL cases with high GLI1 messenger RNA levels, but not

262 Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show

263 1, we demonstrated that one-third of primary T-ALLs were resistant to GCs when cells were cultured in

264 insulated neighborhoods containing prominent T-ALL proto-oncogenes.

265 terations in signaling pathways that promote T-ALL growth, the identity of endogenous stromal cells a

266 nd Akt pathways downstream of Ras in RasGRP1 T-ALL but not in normal thymocytes.

267 patients and murine models, in which RasGRP1 T-ALLs expand in response to treatment with interleukins

268 ctivity is mandatory for fighting refractory T-ALL.

269 e as a novel therapy for relapsed/refractory T-ALL, and that AKR1C3 expression could be used as a bio

270 A patient with refractory T-ALL was treated with dasatinib on the basis of drug pr

271 Moreover, Cic inactivation renders T-ALL insensitive to MEK inhibitors in both mouse and hu

272 invasion by and survival of chemo-resistant T-ALL cells.

273 re able to induce cell death in GC-resistant T-ALL cells, and remarkably, cotreatment with dexamethas

274 novative therapeutic opportunities in SCL(+) T-ALL.

275 th myristoylated AKT developed GSI-sensitive T-ALLs that acquired Notch1 mutations.

276 iffer at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes,

277 DCs support T-ALL growth both in primary thymic tumors and at second

278 y a molecular mechanism by which DCs support T-ALL growth, we first performed gene expression profili

279 cells provide signals that directly support T-ALL cells.

280 s in the tumor microenvironment that support T-ALL remains unknown.

281 DCs, are necessary and sufficient to support T-ALL survival ex vivo.

282 tumor-associated myeloid cells would support T-ALL in vivo.

283 ARIEL is specifically activated in TAL1 (+) T-ALL cases, and its expression is associated with ARID5

284 essive mark is focally diminished in TAL1(+) T-ALLs.

285 Our results reveal that T-ALL cells do not depend on specific bone marrow microe

286 We demonstrated that in these T-ALLs and in distinct populations of normal developing

287 c balance between RasGEF and RasGAP in these T-ALLs and put forth a new model in which IL-2/7/9 decre

288 needed to improve treatment outcomes in this T-ALL/LBL subset.

289 ic antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression

290 directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown.

291 mental conditions, and all are permissive to T-ALL.

292 detected at the promoters of key upregulated T-ALL driver genes (Hhex, Lyl1, and Nfe2) in preleukemic

293 T-acute lymphoblastic leukemia (T-ALL) using T-ALL cell lines and patient-derived samples.

294 h Pdgfrb and Igf1r were activated in ex vivo T-ALL cells, and coculture with tumor-associated, but no

295 However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as s

296 -free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no n

297 of a large cohort of 213 adult patients with T-ALL, including 47 patients with ETP-ALL, treated in th

298 th a higher mutational load in patients with T-ALL, with an enrichment in NOTCH1-activating lesions.

299 g these pathways could benefit patients with T-ALL.

300 A total of 111 patients with T-ALL/LBL (68% T-ALL; 32% T-LBL) with adequate immunophe