ライフサイエンスコーパス: MLL

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

2 MLL-Af4 cells can assume a myeloid state under environme

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

4 MLL-AF4 leukemia is the predominant infant acute leukemi

5 MLL-AF9 and other MLL fusion proteins aberrantly recruit

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

7 MLL-ENL target loci showed supraphysiological PAF1 bindi

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

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

10 1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML.

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

12 nd targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL

13 e expression patterns, including an aberrant MLL signature.

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

15 primary human HSPCs faithfully models acute MLL-rearranged leukemia and provides an experimental pla

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

17 impairs the transforming ability of MLL-AF9, MLL-AF6, and NUP98-NSD1 fusions-mechanistically distinct

18 The rescue of RAS-GTP levels after MLL-AF6 and AF6 co-silencing confirmed that MLL-AF6 onco

19 enhanced antiproliferative activity against MLL-rearranged leukemia cells.

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

21 l unit that interacts with and activates all MLL family histone methyltransferases.

22 R5, RBBP5 and ASH2L, which are shared by all MLL family complexes.

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

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

25 Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusi

26 The leukemic blasts expressed an MLL-associated transcriptional program with elevated lev

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

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

29 genetic or pharmacological inhibition of an MLL downstream target, HOXA9, which activates expression

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

31 e editing to generate endogenous MLL-AF9 and MLL-ENL oncogenes through insertional mutagenesis in pri

32 ACT, PBAF, PAF1C, Mediator, SMC/Cohesion and MLL complexes.

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

34 Hit rate analysis for the CREB-KIX and MLL-KIX sites provided a metric to assess the ligandabil

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

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

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

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

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

40 DNMT3A is dispensable for RUNX1-RUNX1T1- and MLL-AF9-driven self-renewal.

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

42 hment of a heterochromatin-like state around MLL fusion target genes after DOT1L inhibition.

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

44 cially known as KMT2A; herein referred to as MLL to denote the gene associated with mixed-lineage leu

45 acetylation and minimal H3K9 methylation at MLL fusion target genes.

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

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

48 Administration of dinaciclib to mice bearing MLL-AF9-driven human and mouse leukemias elicited potent

49 a well-defined murine leukemia model bearing MLL-AF9.

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

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

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

53 In contrast to infant cases, MLL-R leukemia in older children had more somatic mutati

54 d 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia.

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

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

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

58 protein 5 (WDR5), a core subunit of COMPASS/MLL family histone H3 lysine 4 methyltransferase (H3K4MT

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

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

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

62 , with concomitant downregulation of crucial MLL target genes and the LSC maintenance transcriptional

63 onal program with elevated levels of crucial MLL target genes, displayed heightened sensitivity to DO

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

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

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

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

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

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

70 Despite MLL proteins being postulated as essential for normal de

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

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

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

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

75 Thus, genome editing to create endogenous MLL oncogenes in primary human HSPCs faithfully models a

76 diated genome editing to generate endogenous MLL-AF9 and MLL-ENL oncogenes through insertional mutage

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

78 the mechanistic role of Meis1 in established MLL leukemia.

79 says in MLL-AF9(+) leukemic cells expressing MLL interaction-defective LEDGF/p75 mutants revealed tha

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

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

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

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

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

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

86 lecule compounds as a novel therapeutics for MLL-rearranged leukemia.

87 action represents an effective treatment for MLL leukemias in vivo and provide advanced molecular sca

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

89 se compounds in primary samples derived from MLL leukemia patients.

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

91 -ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and

92 es implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1).

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

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

95 tions affecting mixed lineage leukemia gene (MLL) result in acute leukemias resistant to therapy.

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

97 ciated with mixed-lineage leukemia) generate MLL fusion proteins that bind DNA and drive leukemogenic

98 atic mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients that are a

99 ported to suppress growth of cells harboring MLL-fusions compared to those with alternate oncogenic d

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

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

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

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

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

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

106 regulates leukemogenesis in murine and human MLL-rearranged AML cells, demonstrating a crucial role f

107 ET151 in vivo using mice injected with human MLL-fusion leukemia cells and evaluated disease progress

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

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

110 Colony-forming assays in MLL-AF9(+) leukemic cells expressing MLL interaction-def

111 d MI-503, and show their profound effects in MLL leukemia cells and substantial survival benefit in m

112 We report that LSCs in MLL-associated leukemia reside in an epigenetic state of

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

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

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

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

117 scent leukemia-initiating cell population in MLL-rearranged AML, providing opportunities for selectiv

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

119 1 expression and attenuated proliferation in MLL-AF9 cells.

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

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

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

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

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

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

126 ception of MLL, was rarely mutated in infant MLL-R ALL.

127 Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic m

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

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

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

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

132 menin and oncogenic mixed lineage leukemia (MLL) fusion proteins is required for leukemic transforma

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

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

135 ements involving the mixed-lineage leukemia (MLL) gene occur in primary and treatment-related leukemi

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

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

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

139 earrangements of the mixed-lineage leukemia (MLL) gene.

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

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

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

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

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

145 A translation of the mixed lineage leukemia (MLL) proto-oncogene in an arginine methylation-dependent

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

147 rectly maintains the mixed-lineage leukemia (MLL) self-renewal program by interacting with and retain

148 4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner.

149 ective treatment for mixed-lineage leukemia (MLL)-fusion leukemia' by Dawson and colleagues, publishe

150 mising new target in mixed lineage leukemia (MLL)-rearranged acute myeloid leukemia (AML) and show th

151 d inhibits growth of mixed lineage leukemia (MLL)-rearranged leukemia cells.

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

153 , leukemia driven by mixed-lineage leukemia (MLL, encoded by KMT2A) fusions with dominant transactiva

154 iology of rearranged mixed lineage leukemia (MLL-r).

155 depleted in murine acute myeloid leukemias (MLL-AF9;Nras(G12D); PML-RARalpha acute promyelocytic leu

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

157 carbonyls may improve the activity of menin-MLL inhibitors as much as 5- to 10-fold.

158 sites in the thienopyrimidine class of menin-MLL inhibitors considerably improved their inhibitory ac

159 ent with a small-molecule inhibitor of menin-MLL interaction blocks AR signaling and inhibits the gro

160 Analysis of the menin-MLL inhibitor complexes revealed that the backbone in se

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

162 e that pharmacologic inhibition of the menin-MLL interaction represents an effective treatment for ML

163 lable small-molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, and show their profo

164 interacts with the MLL complex via the menin-MLL subunit.

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

166 impairs growth and colony formation of mouse MLL-AF9 cells in vitro as well as establishment of leuke

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

168 , and for the clonogenic potential of murine MLL-AF9 AML cells.

169 Using murine MLL-AF9 and MOZ-TIF2 AML models, we show that myeloid di

170 equencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with le

171 R3 methyltransferase, in various MLL and non-MLL leukemias.

172 transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant

173 ion, and impairs the transforming ability of MLL-AF9, MLL-AF6, and NUP98-NSD1 fusions-mechanistically

174 The leukemogenic activity of MLL fusion proteins is dependent on their interaction wi

175 f how these factors regulate the activity of MLL proteins still remains poorly understood.

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

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

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

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

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

181 Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decre

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

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

184 to growth inhibition and differentiation of MLL-driven leukemic cells.

185 rotein (MLL) complex, a well-known driver of MLL fusion-positive leukemia, acts as a co-activator of

186 ing protein JMJD1C as an important driver of MLL-AF9 leukemia.

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

188 e data identify CDK6 as critical effector of MLL fusions in leukemogenesis that might be targeted to

189 ategory of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.

190 Exposure of MLL-AF6-rearranged AML blasts to tipifarnib, a RAS inhib

191 xenograft models demonstrated inhibition of MLL-r tumor growth and inhibition of pharmacodynamic mar

192 ostnatal hematopoiesis and the initiation of MLL leukemogenesis.

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

194 2 in a murine model decreased the latency of MLL-AF9-induced leukemia and caused resistance to cytara

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

196 es reveal a two-step activation mechanism of MLL family proteins.

197 establish JMJD1C as an important mediator of MLL-AF9- and HOXA9-driven LSC function that is largely d

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

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

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

201 stantial survival benefit in mouse models of MLL leukemia.

202 from genetically engineered mouse models of MLL-AF9-driven acute myeloid leukemia (AML).

203 urther evaluation in rat xenograft models of MLL-r leukemia.

204 ype and prolong survival in murine models of MLL-rearranged leukemia.

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

206 valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.

207 The pathogenesis of MLL-fusion leukemias has been linked to upregulation of

208 reduced the leukemia-initiating potential of MLL-AF9(+) acute myeloid leukemia cells in a dose-depend

209 it determined the transforming potential of MLL-ENL.

210 ential for the initiation and propagation of MLL-ENL-induced AML but dispensable for normal myelopoie

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

212 Rearrangements of MLL (encoding lysine-specific methyltransferase 2A and o

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

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

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

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

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

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

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

220 In Figure 3D, treatment of MLL-fusion leukemia cells with I-BET151 resulted in tran

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

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

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

224 substantially advanced our understanding of MLL leukemia pathogenesis, but often use supraphysiologi

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

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

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

228 urvival in retrovirally induced Myc-Bcl2- or MLL-AF9-driven leukemia, and acute myeloid leukemia (AML

229 ctors to express PML-RARA, RUNX1-RUNX1T1, or MLL-AF9 in bone marrow cells derived from WT or DNMT3A-d

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

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

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

233 r cells immortalized with the fusion protein MLL-AF9 to generate several single-cell clones that demo

234 ate that the mixed-lineage leukemia protein (MLL) complex, a well-known driver of MLL fusion-positive

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

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

237 the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%.

238 stic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor progno

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

240 -lineage leukemia breakpoint cluster region (MLL BCR).

241 Upon dietary restriction, MLL-AF9-induced murine acute myeloid leukemia (AML) acti

242 chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investiga

243 associated genes, impairs DDR and sensitizes MLL leukemia to PARP inhibitors (PARPis).

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

245 MLL-AF6 and AF6 co-silencing confirmed that MLL-AF6 oncoprotein potentiates the activity of the RAS

246 netics, Andersson and colleagues report that MLL fusion alone may be sufficient to spawn an aggressiv

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

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

249 or without MLL translocations, showing that MLL translocations cause a hypomorph phenotype of RUNX1/

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

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

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

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

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

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

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

257 ification of a minimal pharmacaphore for the MLL-KIX interaction site.

258 Taken together, this work identifies the MLL complex as a crucial co-activator of AR and a potent

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

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

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

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

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

264 as (AMLs) with genomic rearrangements of the MLL gene contain a non-quiescent LSC population.

265 a carrying chromosomal translocations of the MLL gene.

266 as marked by oncogenic rearrangements of the MLL gene.

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

268 r findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpressio

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

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

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

272 AR directly interacts with the MLL complex via the menin-MLL subunit.

273 relieves the cellular oncogenic addiction to MLL chimeras.

274 ecruitment of the transcription machinery to MLL target genes.

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

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

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

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

279 PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias.

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

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

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

283 fant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemi

284 CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations.

285 ly and specifically upregulated in AMLs with MLL translocations.

286 ant gene expression programs associated with MLL-fusion leukemia.

287 me the differentiation block associated with MLL-rearranged AML, and underscore that cell-cycle regul

288 tem in human established leukemic cells with MLL-AF9 translocation have no impact on their functions.

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

290 mation and that C/EBPalpha collaborates with MLL-ENL in the induction of a transcriptional program, w

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

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

293 d inducible Meis1-knockout mice coupled with MLL-AF9 knockin mice to decipher the mechanistic role of

294 childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overal

295 Leukemias with MLL translocations are often found in infants and are as

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

297 lymphoblastic leukemias, such as those with MLL and BCR/ABL abnormalities, and correlate with the en

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

299 d leukemia (AML) cell lines, with or without MLL translocations, showing that MLL translocations caus

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