ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/003/SRR2005803/SRR2005803_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/000/SRR2005800/SRR2005800_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/003/SRR2005793/SRR2005793.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/001/SRR2005791/SRR2005791.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/001/SRR2005801/SRR2005801_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/002/SRR2005802/SRR2005802_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/007/SRR2005797/SRR2005797_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/003/SRR2005803/SRR2005803_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/002/SRR2005802/SRR2005802_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/001/SRR2005801/SRR2005801_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/005/SRR2005795/SRR2005795.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/004/SRR2005804/SRR2005804_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/009/SRR2005799/SRR2005799_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/008/SRR2005798/SRR2005798_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/002/SRR2005792/SRR2005792.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/006/SRR2005796/SRR2005796.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/004/SRR2005804/SRR2005804_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/008/SRR2005798/SRR2005798_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/007/SRR2005797/SRR2005797_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/004/SRR2005794/SRR2005794.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/000/SRR2005800/SRR2005800_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR200/009/SRR2005799/SRR2005799_1.fastq.gzprimaryOK200GenomicsGene Regulation, Research, Peter MacCallum Cancer Centrehttps://www.ebi.ac.uk/ena/browser/view/PRJNA282927Mus musculusxref:PubMed:27374225We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. To compare gene expression changes associated with enforced Id2 expression and MLL-AF9 withdrawal, RNA sequencing analysis was performed on Tet-off MLL-AF9 cells transduced with an Id2 over-expressing or a control vector, or upon MLL-AF9 dox-inducible knock-down. Overall design: Primary AMLs driven by Tet-off inducible MLL/AF9 expression linked to dsRED reporter, in association with oncogenic NRASG12D (Tet-off MLL-AF9) were generated by reconstituting lethally irradiated congenic mice with foetal liver cells co-transduced with a Tet-Off-MLL-AF9-dRED retroviral vector and a second vector co-expressing NRASG12D together with the Tet-Off responsive transcriptional activator. RNA sequencing analysis sequencing analysis was performed on Tet-Off MLL-AF9/dsRED+ AML cells treated in vitro with doxycycline (DOX) for 4 days to inactivate MLL-AF9 expression or left untreated (UT). For the Id2 over-expression experiment, Tet-Off MLL-AF9/dsRED+ AML cells were transduced in vitro with an Id2-GFP or a control-GFP retroviral vector. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis.ENAMyelogenous Leukemias, Myelocytic, HTRX1, Tet, Acute Myeloblastic, Id-2, acute myeloblastic leukemia, RNA Sequence Determination, determination, Nonlymphocytic Leukemia, acute non lymphoblastic leukemia, Myeloid, acute myeloblastic leukaemia, BHLHB26, Sequence Determination, acute myelogenous leukaemia, RNA Sequence, NS6, Myelocytic Leukemia, GIG8, MLL|GAS7, thymoma, nap, MLL1A, Acute Myeloid, Cxxc7, Acute Myelocytic Leukemias, C78922, 2610012I03Rik, acute non lymphoblastic leukaemia, ALPS4, Acute Myelocytic, Acute Nonlymphoblastic, acute myeloid, Analysis, AI255428, Myeloblastic Leukemia, adult, NCMS, N-ras, Leukemia, Analyses, Determination, Acute Myelogenous, Acute Myeloblastic Leukemia, ALL-1, Myelogenous Leukemia, mak, Acute Nonlymphocytic Leukemias, Sequence Determinations, Sequencing, Af-9., Mll1, MLL1, Acute Myeloid Leukemia without Maturation, 6430520K01, Acute Nonlymphoblastic Leukemia, RNA Sequence Analyses, Acute Nonlymphocytic Leukemia, Ac2-300, Myeloid Leukemia, Myelocytic Leukemias, RNA Sequencing, ANLL, YEATS3, Nonlymphoblastic Leukemias, 3830408D16Rik, Sequence Analyses, acute myelogenous, leukemia, Myelogenous, RNA, M1, 2210011H10Rik, M2, MLE, acute myelogenous leukemia, ID2A, NRAS1, RNA Sequence Determinations, Mll, MLL, HRX, ID2H, bHLHb26, Af9, CG11680, MLL/GAS7, Leukemias, Cell, id2-A, Determinations, AML, Acute Myelocytic Leukemia, Nonlymphoblastic Leukemia, Nonlymphocytic Leukemias, Nonlymphoblastic, Acute Myeloid Leukemias, Idb2, DmelCG11680, mll, chemical analysis, Af-9, Myeloid Leukemias, CMNS, AF9, mls, Acute Nonlymphocytic, Acute Myelogenous Leukemia, TET1-MLL, acute, Acute myelogenous leukemia, D4Ertd321e, Myeloblastic, CXXC7, All1, WDSTS, susceptibility to, Myeloblastic Leukemias, NRAS, Acute Myeloid Leukemia, acute myeloid leukemia, acute myeloid leukaemia, XId2, Nonlymphocytic, mKIAA4050, Acute Myeloid Leukemia with Maturation, Acute, nap[ts], Acute Nonlymphoblastic Leukemias, Acute Myeloblastic Leukemias, RNA Sequence Analysis, Acute Myelogenous Leukemias, TRX1, assay, AV095280, AML - acute Myeloid LeukemiaMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusRNA sequencing expression analysis of murine Tet-off MLL-AF9 NRAS acute myeloid leukemia cells over-expressing Id2 and upon MLL-AF9 withdrawal2025-09-242016-10-10PRJNA282927GSE684621009027374225