ライフサイエンスコーパス: MLL

1 and therapy-induced mixed lineage leukemia (MLL).

2 ge of MLL1 results in the destabilization of MLL.

3 ug/mLl and SHIVAD8 with an IC50 of 0.028 ug/mLl.

4 er cells and at the translocation 'hotspot', MLL.

5 Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcription by aberra

6 The MLL-AF4 (MA4) fusion gene is the genetic hallmark of an

7 MLL-Af4 activated a self-renewal program in a lineage-de

8 -throughput sequencing) analyses showed that MLL-AF4 and MLL-ENL fusions directly bound to the BCL6 p

9 l precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALL

10 ia gene (MLL) rearrangements (MLL-r) such as MLL-AF4 are a major cause of incurable acute lymphoblast

11 In contrast, MLL-Af4 cells, which were fully oncogenic under lymphoid

12 MLL-Af4 induces a B ALL distinct from MLL-AF9 through di

13 ogenitor cells (HSPCs) expressing MLL-AF9 or MLL-Af4 into immunodeficient NSGS mice, which strongly p

14 Using the DOT1L inhibitor EPZ-5676 in MLL-AF4 leukemia cells, we show that H3K79me2/3 is requi

15 onal role at a subset of active enhancers in MLL-AF4 leukemia cells.

16 MLL-AF4 leukemia is the predominant infant acute leukemi

17 bute to the strong B-cell ALL association of MLL-AF4 leukemia observed in the clinic.

18 e self-renewal ability and leukemogenesis of MLL-Af4 myeloid cells could contribute to the strong B-c

19 manner, showing the leukemogenic activity of MLL-Af4 was interlinked with lymphoid lineage commitment

20 a genome-scale loss-of-function screen in an MLL-AF4-positive acute leukaemia cell line, we identify

21 c ablation of CDC42 in both murine and human MLL-AF9 (MA9) cells decreased survival and induced diffe

22 for survival, quiescence and self-renewal of MLL-AF9 (MA9)-transformed leukemia stem cells (LSCs) in

23 proteins regardless of matrix stiffness when MLL-AF9 and BCR-ABL are overexpressed in K-562 and MOLM-

24 his signature, SOCS2, was investigated using MLL-AF9 and Flt3-ITD/NPM1c driven mouse models of AML.

25 MLL-AF9 and other MLL fusion proteins aberrantly recruit

26 PAR-1 increased the adherence properties of MLL-AF9 cells and promoted their engraftment to bone mar

27 72 triggers immune-inflammatory responses in MLL-AF9 cells including upregulation of Hif1alpha and PD

28 1 expression and attenuated proliferation in MLL-AF9 cells.

29 activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells.

30 Cells expressing MLL-AF9 efficiently developed AML in NSGS mice.

31 MLL-AF9 expression in long-term hematopoietic stem cells

32 opoulou et al. report that expression of the MLL-AF9 fusion results in acute myelogenous leukemia (AM

33 arkable anticlonogenic cell growth effect on MLL-AF9 human leukemia cells.

34 e HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML s

35 blocked the growth of both murine and human MLL-AF9 leukemia cell lines.

36 We show that MLL-AF9 leukemia cells maintain cell polarity in the con

37 mia development induced by a small number of MLL-AF9 leukemia stem cells (LSCs) in vivo.

38 ted the cell-dose-dependent role of PAR-1 in MLL-AF9 leukemia: PAR-1 inhibited rapid leukemic prolife

39 n accessibility, and direct IKZF2 binding in MLL-AF9 LSCs demonstrate that IKZF2 regulates a HOXA9 se

40 In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decrea

41 Accordingly, inhibition of CKII in a MLL-AF9 mouse model of leukemia delayed leukemic progres

42 Using an MLL-AF9 murine leukemia model and serial transplantation

43 n a syngeneic murine AML model driven by the MLL-AF9 oncogenic fusion protein.

44 stem and progenitor cells (HSPCs) expressing MLL-AF9 or MLL-Af4 into immunodeficient NSGS mice, which

45 Molecularly, we propose that MLL-AF9 preserves gene expression of the cellular states

46 MLL-Af4 induces a B ALL distinct from MLL-AF9 through differential genomic target binding of t

47 tion in human leukemia cell lines possessing MLL-AF9 translocations.

48 rease in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells.

49 some acute myeloid leukemia types, including MLL-AF9(+) MOLM-14 cells, in a biphasic manner by autocr

50 When driven by MLL-AF9, leukemia cells in the adult microenvironment su

51 ing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneit

52 LSC frequency and caused differentiation of MLL-AF9- and homeobox A9-driven (HOXA9-driven) leukemias

53 S-5272, causes dramatic tumor regressions of MLL-AF9-driven AML in vivo with a tolerable toxicity.

54 ated an inducible transgenic mouse model for MLL-AF9-driven leukemia.

55 ditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and p

56 uced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction

57 GVL against 2 acute myeloid leukemia lines (MLL-AF9-eGFP and C1498-luciferase).

58 orable acute GVHD and GVL properties against MLL-AF9-eGFP cells.

59 se model of AML, the loss of Cdc42 abrogates MLL-AF9-induced AML development.

60 s of Runx1/Cbfb inhibited the development of MLL-AF9-induced AML.

61 2 in a murine model decreased the latency of MLL-AF9-induced leukemia and caused resistance to cytara

62 RDM16 by DNA methylation is concomitant with MLL-AF9-induced leukemic transformation.

63 ced leukemias, preferentially at gene bodies.MLL-AF9-induced leukemogenesis showed much less pronounc

64 vely correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition of the above si

65 regulator of HSC function, which facilitates MLL-AF9-mediated leukemic disease in mice.

66 improved survival in mice transplanted with MLL-AF9-positive leukemic stem cells by modulating AKT a

67 lone had a significant impact on survival of MLL-AF9-transformed cells, and additional Mll1 loss furt

68 n genes such as PML-RARA, RUNX1-RUNX1T1, and MLL-AF9.

69 mixed lineage leukemia (MLL) fusion oncogene MLL-AF9.

70 inct transcriptional profiles within LSCs of Mll-AF9/NRAS(G12V) murine AML were identified using sing

71 e mRNA level from the wild-type and chimeric MLL alleles, the chimeric protein is more stable.

72 suggesting a positive feedback loop between MLL and BCL6.

73 Our data suggest that combined menin-MLL and FLT3 inhibition represents a novel and promising

74 s the impact of different reference systems (MLL and HAKE) in the absolute-relative and relative quan

75 IP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell program.

76 is complex contributes to the association of MLL and MLL-fusion multiprotein complexes with the chrom

77 The N-terminus of MLL and MLL-fusions form a complex with lens epithelium-

78 etoposide-induced chromosomal breaks at the MLL and RUNX1 loci.

79 panel with a geometric mean IC50 of 0.055 ug/mLl and SHIVAD8 with an IC50 of 0.028 ug/mLl.

80 ment, whereas AML cells with wild-type NPM1, MLL, and FLT3 were not affected by either of the 2 drugs

81 ed using a relative quantification approach (MLL as reference system).

82 mplexes and inhibited chromatin occupancy of MLL at select genes.

83 ent of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy.

84 Loss of MLL binding led to changes in gene expression, different

85 nary complex with BMAL1, indicating that the MLL-binding pocket is important for KIX-BMAL1 interactio

86 37) Tethering the small compound 1-10 in the MLL-binding pocket of the CBP-KIX domain weakened BMAL1

87 suggested that the G-region emerges near the MLL-binding pocket, further supporting a role of this po

88 Although the MLL-CHD fusion protein failed to immortalize HSPCs in my

89 g wild-type MLL protein, which displaces the MLL chimera from some of its target genes and, therefore

90 ates a specific group of target genes of the MLL chimeras and their oncogenic cofactor, the super elo

91 eaved MLL1 can result in the displacement of MLL chimeras from chromatin in leukemic cells.

92 lity, and results in the displacement of the MLL chimeras from chromatin.

93 ixed-lineage leukemia 1 (MLL1) gene generate MLL chimeras that drive the pathogenesis of acute myeloi

94 relieves the cellular oncogenic addiction to MLL chimeras.

95 Although MLL/COMPASS (complex of proteins associated with Set1) f

96 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromat

97 e is known about cellular factors modulating MLL complex activity.

98 rt sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and

99 fter pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression

100 Dysregulation of MLL complex-mediated histone methylation plays a pivotal

101 ly known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation.

102 tudies, the molecular mechanisms whereby the MLL complexes recognize histone H3K4 within nucleosome c

103 s involving the mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both

104 Hoxa9 that is highly enriched in LSK-derived MLL-CSCs and helps sustain leukemic self-renewal.

105 s beta-catenin-independent transformation in MLL-CSCs derived from hematopoietic stem cell (HSC)-enri

106 Suppression of Hoxa9 sensitizes LSK-derived MLL-CSCs to beta-catenin inhibition resulting in abolish

107 beta-catenin/Hoxa9 functions in LSK-derived MLL-CSCs.

108 Targeting wild-type MLL degradation impedes MLL leukemia cell proliferation,

109 These findings uncover MLL-dependent transcriptional activation of BCL6 as a pr

110 partners, identifying the novel fusion gene MLL-DIAPH2 in the process.

111 Here, we have shown that MLL-ENL and MLL-AF10 constitutively activate transcripti

112 early cellular and molecular consequences of MLL-ENL expression based on a clear clonal relationship

113 sequencing) analyses showed that MLL-AF4 and MLL-ENL fusions directly bound to the BCL6 promoter and

114 In MLL-ENL leukemia, the neonatal microenvironment potentia

115 MLL-ENL target loci showed supraphysiological PAF1 bindi

116 it determined the transforming potential of MLL-ENL.

117 complex assembly and activity regulation of MLL family methyltransferases, and also suggest a univer

118 are two closely related members of the SET1/MLL family of histone H3K4 methyltransferases and are re

119 complex represents the prototype of the SET1/MLL family of methyltransferases that controls gene tran

120 Mixed lineage leukemia (MLL) family histone methyltransferases are enzymes that

121 is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1

122 The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and

123 In addition, MLL-FP driven acute myeloid leukemia (AML) in mice is of

124 have very few cooperating mutations, making MLL-FP driven leukemias ideal for animal modeling.

125 The fact that the MLL-FP is the main driver mutation has allowed for a wid

126 ogical insights each model has provided into MLL-FP leukemogenesis.

127 ems designed to explore different aspects of MLL-FP leukemogenesis.

128 Lessons learned from past and present MLL-FP models may serve as a paradigm for designing more

129 his review provides an overview of different MLL-FP mouse model systems and discusses how well they h

130 Patients carrying MLL-FPs have very few cooperating mutations, making MLL-

131 artner genes creating novel fusion proteins (MLL-FPs) that cause aggressive acute leukemias in humans

132 Here we show that MLL fused to murine Af4, highly conserved with human AF4

133 for the treatment of acute leukemia carrying MLL fusion (MLL leukemia).

134 for the treatment of acute leukemia carrying MLL fusion (MLL leukemia).

135 CND1 expression predicts worse prognosis for MLL fusion AMLs.

136 volvement of chromatin-associated factors as MLL fusion partners belies a dependency on transcription

137 DM16 is required for specific suppression of MLL fusion protein-induced leukemogenesis both in vitro

138 MLL-AF9 and other MLL fusion proteins aberrantly recruit epigenetic regula

139 vator complex that makes direct contact with MLL fusion proteins and is involved in AML, however, its

140 rotein-protein interaction between menin and MLL fusion proteins that plays an important role in acut

141 of CDK inhibitors in AML patients harboring MLL fusion proteins.

142 ;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC(50) values of 25 and 55 nM, respectiv

143 onale for the simultaneous inhibition of the MLL fusion-AF4 complex and DOT1L for more effective trea

144 ty over the HL-60 leukemia cell line lacking MLL fusion.

145 3 and is involved in Mixed Lineage Leukemia (MLL) fusion leukemogenesis; however, its role in prostat

146 enesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9.

147 We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the B

148 t to chromatin as an effective treatment for MLL-fusion leukaemia".

149 The lineage decision of MLL-fusion leukemia is influenced by the fusion partner

150 ex contributes to the association of MLL and MLL-fusion multiprotein complexes with the chromatin.

151 neage leukemia (MLL) to AF4, the most common MLL-fusion partner.

152 the mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both acute lympho

153 s demonstrating that MLL1 is dispensable for MLL-fusion-mediated leukemogenesis.

154 NIN and LEDGF/p75 are required for efficient MLL-fusion-mediated transformation and for the expressio

155 ent of malignant transformation by oncogenic MLL fusions and identified BCL6 as a novel target for th

156 While oncogenic MLL fusions strongly induced aberrant BCL6 expression in

157 Oncogenic MLL fusions strongly induced transcriptional activation

158 provided a constitutive PAF1 tether allowing MLL fusions to circumvent H3 competition.

159 stem cells (CSCs) including those driven by MLL fusions, here we show that transcriptional memory fr

160 The N-terminus of MLL and MLL-fusions form a complex with lens epithelium-derived

161 a carrying chromosomal translocations of the MLL gene.

162 as marked by oncogenic rearrangements of the MLL gene.

163 ations involving the mixed lineage leukemia (MLL) gene fuse it in frame with multiple partner genes c

164 ranslocations of the mixed lineage leukemia (MLL) gene occur in 60% to 80% of all infant acute leukem

165 earrangements of the mixed lineage leukemia (MLL) gene occur in ~10% of B-cell acute lymphoblastic le

166 The mixed-lineage leukemia (MLL) gene often fuses with ENL and AF10 family genes in

167 e acute leukemias, notably those with KMT2A (MLL) gene rearrangements.

168 rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells.

169 ranslocations of the mixed-lineage leukemia (MLL) gene with various partner genes result in aggressiv

170 of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 v

171 In vitro studies identified SET1/MLL histone methyltransferases as redox sensitive units

172 , a component of the mixed-lineage leukemia (MLL) histone methyltransferase complex, and transcriptio

173 eveloped and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional ev

174 ons in regulating the stability of wild-type MLL in response to interleukin-1 signaling.

175 It is fused to mixed-lineage leukemia (MLL) in leukemia, and missense mutations have been ident

176 olecule BIM, while BCL6 was required to curb MLL-induced expression of BIM.

177 Combining menin-MLL inhibition with specific small-molecule kinase inhib

178 A new orally bioavailable Menin-MLL inhibitor (VTP-50469) appears to promote their diffe

179 ructure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing in

180 sing preclinical studies with XPO1 and menin-MLL inhibitors.

181 ss of small-molecule inhibitors of the menin-MLL interaction (hereafter called menin inhibitors).

182 esents the most potent inhibitor of the WDR5-MLL interaction reported to date, and further optimizati

183 hronic transplantation of leukemia driven by MLL/KMT2A translocations to investigate the contribution

184 n = 14) in an EC enriched with patients with MLL/KMT2A-rearranged AML.

185 These data corroborate the MLL-LEDGF/p75 interaction as novel target for the treatm

186 the development of therapies for aggressive MLL leukemia and perhaps for other cancers caused by tra

187 Targeting wild-type MLL degradation impedes MLL leukemia cell proliferation, and it downregulates a

188 tment of acute leukemia carrying MLL fusion (MLL leukemia).

189 tment of acute leukemia carrying MLL fusion (MLL leukemia).

190 eveloping a new therapy for the treatment of MLL leukemia.

191 ated a pronounced effect in a mouse model of MLL leukemia.

192 a new class of therapy for the treatment of MLL leukemia.

193 ostnatal hematopoiesis and the initiation of MLL leukemogenesis.

194 bout the specific functions of the different MLL lysine methyltransferases.

195 opoiesis but essential for the initiation of MLL-mediated leukemia.

196 Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic

197 The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potenti

198 mutations favoring PAF1 binding, whereas the MLL moiety provided a constitutive PAF1 tether allowing

199 -BET151 efficacy in a disseminated xenograft MLL mouse model, whereas the original study reported inc

200 Inducible expression of Bcl6 increased MLL mRNA levels, which was reversed by genetic deletion

201 Absolute quantification using the MLL nuclear system has been demonstrated as appropriate

202 the hematopoietic stem cells, and decreased MLL occupancy at MLL target genes.

203 mosomal translocations producing a chimaeric MLL oncogene give rise to a highly aggressive acute leuk

204 internal-tandem and mixed-lineage leukemia (MLL) partial-tandem duplications, and clinically signifi

205 urine leukemia through stabilizing wild-type MLL protein, which displaces the MLL chimera from some o

206 Targeting the menin-MLL protein-protein interaction is a new therapeutic str

207 ibition of the menin-mixed lineage leukemia (MLL) protein-protein interaction is a promising new ther

208 ) and block the WDR5-mixed lineage leukemia (MLL) protein-protein interaction.

209 Despite MLL proteins being postulated as essential for normal de

210 ylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regula

211 Stabilization of MLL provides us with a paradigm in the development of th

212 with either MLL-r acute myeloid leukemia or MLL-r acute lymphoblastic leukemia (ALL) showed dramatic

213 DX) models derived from patients with either MLL-r acute myeloid leukemia or MLL-r acute lymphoblasti

214 ere, we demonstrate elevated PRMT1 levels in MLL-r ALL cells and show that inhibition of PRMT1 signif

215 73 (R972/973), and its oncogenic function in MLL-r ALL cells is FLT3 methylation dependent.

216 with MS023 treatment enhanced elimination of MLL-r ALL cells relative to PKC412 treatment alone in pa

217 on represents a promising strategy to target MLL-r ALL cells.

218 Thus, defining mechanisms underlying MLL-r ALL maintenance is critical for developing effecti

219 Multiple mice engrafted with MLL-r ALL remained disease free for more than 1 year aft

220 In vivo treatment of leukemic animals with MLL-r FLT3mut leukemia reduced leukemia burden significa

221 peutic strategy for patients with NPM1mut or MLL-r leukemia and concurrent FLT3 mutation.

222 nt in models of human and murine NPM1mut and MLL-r leukemias harboring an FLT3 mutation.

223 haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular conse

224 se remains the main cause of MLL-rearranged (MLL-r) acute lymphoblastic leukemia (ALL) treatment fail

225 ial therapeutic strategy for MLL-rearranged (MLL-r) leukemia.

226 of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias.

227 lineage leukemia gene (MLL) rearrangements (MLL-r) such as MLL-AF4 are a major cause of incurable ac

228 X) of pediatric mixed-lineage leukemia gene (MLL)-rearranged ALL were established in NOD.Cg-Prkdc(sci

229 ients suffering from mixed lineage leukemia (MLL)-rearranged leukemia remain below 50% and more targe

230 tain cancers such as mixed-lineage leukemia (MLL)-rearranged leukemias.

231 Relapse remains the main cause of MLL-rearranged (MLL-r) acute lymphoblastic leukemia (ALL

232 tion is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia.

233 y for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias.

234 in relapsed acute lymphoblastic leukemia and MLL-rearranged acute leukemia.

235 Here we use a well-defined model of MLL-rearranged acute myeloid leukaemia (AML) to demonstr

236 MLL-rearranged acute myeloid leukemia (AML) remains a fa

237 expression was also variable in a pediatric MLL-rearranged ALL patient dataset, highlighting the exi

238 l models in vitro, as well as in the in vivo MLL-rearranged AML BMT model coupled with treatment of "

239 nstrate that AMPK maintains the epigenome of MLL-rearranged AML by linking acetyl-coenzyme A (CoA) ho

240 x5 was further confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as in t

241 l and induces apoptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xeno

242 ch to potentially overcome the resistance of MLL-rearranged AML to conventional chemotherapies and pr

243 d that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediate

244 sensitizer, with a therapeutic potential, in MLL-rearranged AML.

245 uiescence, and promoting LSC self-renewal in MLL-rearranged AML.

246 c target for selectively eliminating LSCs in MLL-rearranged AML.

247 a identified CCI-006 as a novel inhibitor of MLL-rearranged and CALM-AF10 translocated leukemias that

248 present a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate

249 with the BH3-mimetic ABT-199 in eradicating MLL-rearranged B-ALL cells.

250 d sensitivity to vincristine chemotherapy in MLL-rearranged B-ALL patient samples.

251 Highlighting the central role of BCL6 in MLL-rearranged B-ALL, conditional deletion and pharmacol

252 BCL6 as a novel target for the treatment of MLL-rearranged B-ALL.

253 a randomized phase 2-like PDX trial using 13 MLL-rearranged BCP-ALL samples.

254 eatment option for infants and children with MLL-rearranged BCP-ALL who have a poor outcome when trea

255 and histone demethylases in AML, especially MLL-rearranged leukaemia.

256 de the basis for a new therapeutic target in MLL-rearranged leukemia and act as further validation of

257 ht the relevance of MLL2 as a drug target in MLL-rearranged leukemia and suggest its broader signific

258 ion and apoptosis in a subset (7/11, 64%) of MLL-rearranged leukemia cell lines within a few hours of

259 ion sensitized an intrinsically unresponsive MLL-rearranged leukemia cell to CCI-006, indicating that

260 also observe an unexpected role for MLL2 in MLL-rearranged leukemia cells and identify potential the

261 ed a novel small molecule that rapidly kills MLL-rearranged leukemia cells by targeting a metabolic v

262 The unresponsive MLL-rearranged leukemia cells did not undergo mitochondr

263 In addition, unresponsive MLL-rearranged leukemia cells expressed increased levels

264 son to the sensitive cells, the unresponsive MLL-rearranged leukemia cells were characterized by a mo

265 subset of low HIF1alpha/low MEIS1-expressing MLL-rearranged leukemia cells.

266 o discover cytotoxic compounds selective for MLL-rearranged leukemia identified CCI-006 as a novel in

267 ntly impairs propagation of murine and human MLL-rearranged leukemia in vitro and in vivo.

268 viously undescribed metabolic variability in MLL-rearranged leukemia that may contribute to the heter

269 wareness of the biologic features underlying MLL-rearranged leukemia, targeted therapies for this leu

270 ist on the requirement for wild-type MLL1 in MLL-rearranged leukemia.

271 raction as novel target for the treatment of MLL-rearranged leukemia.

272 ex and DOT1L for more effective treatment of MLL-rearranged leukemia.

273 els, that endogenous MLL1 is dispensable for MLL-rearranged leukemia.

274 e splicing, is consistently overexpressed in MLL-rearranged leukemias.

275 F inhibitors as a targeted approach to treat MLL-rearranged leukemias.

276 Treatment of MLL-rearranged leukemic cells with dinaciclib resulted i

277 several genes including those essential for MLL-rearranged leukemogenesis, such as DOT1L and SETD1A.

278 ressed in mixed lineage leukemia-rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL),

279 al targeted therapy for AML patients with an MLL rearrangement and an FLT3-ITD.

280 s (iPSCs) from AML patient samples harboring MLL rearrangements and found that they retained leukemic

281 Cell lines carrying MLL rearrangements were selectively responsive to VTP504

282 TO is highly expressed in AMLs with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or

283 Mixed lineage leukemia gene (MLL) rearrangements (MLL-r) such as MLL-AF4 are a major

284 1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML.

285 rmation and for the expression of downstream MLL-regulated genes such as HOXA9 and MEIS1 In light of

286 Mixed lineage leukemia (MLL) represents a genetically distinct and aggressive su

287 e expression patterns, including an aberrant MLL signature.

288 ication approaches, showing that the nuclear MLL system performed better than the mitochondrial HAKE

289 d levels of MEIS1, an important leukemogenic MLL target gene that plays a role in regulating metaboli

290 c stem cells, and decreased MLL occupancy at MLL target genes.

291 ecruitment of the transcription machinery to MLL target genes.

292 4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner.

293 ifferentiation of leukemic stem cells in the MLL-translocated molecular subtype of acute myeloid leuk

294 rowth in human leukemia cell lines harboring MLL translocations and is >40 times better than the prev

295 ificant chromosomal rearrangements including MLL translocations to known and unknown partners, identi

296 ly and specifically upregulated in AMLs with MLL translocations.

297 erentiation, in particular, in patients with MLL translocations.

298 ys an important role in acute leukemias with MLL translocations.

299 ment of aggressive leukemia as the result of MLL translocations.

300 nt of acute myeloid leukemia (AML) harboring MLL translocations.

301 ant BCL6 expression in B-ALL cells, germline MLL was required to up-regulate Bcl6 in response to phys