EXPERIMENT_TITLE: HiC of ChiPSC22 with translocation t(7;12) differentiated into HSPC
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Acute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in veryyoung children and has a poor outcome. The expected oncofusion between breakpointpartners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universalfeature is the strong transcript and protein expression of MNX1, a homeobox transcriptionfactor that is normally not expressed in hematopoietic cells. Here, we map the translocationbreakpoints on chromosomes 7 and 12 in affected patients to a region downstream of MNX1and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML(n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13)AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel anenhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Ourdata suggest that enhancer-hijacking is a more common and overlooked mechanism forstructural rearrangement-mediated gene activation in AML.
SAMPLE_TITLE: translocation_HSPC
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "isolate", "VALUE": "Cell line"}, {"TAG": "age", "VALUE": "32 years"}, {"TAG": "biomaterial_provider", "VALUE": "Cellartis/Takara Bio Europe AB"}, {"TAG": "collection_date", "VALUE": "2022"}, {"TAG": "geo_loc_name", "VALUE": "Germany"}, {"TAG": "sex", "VALUE": "male"}, {"TAG": "tissue", "VALUE": "reprogrammed fibroblast"}, {"TAG": "cell_line", "VALUE": "ChiPSC22"}, {"TAG": "cell_type", "VALUE": "HSPC"}, {"TAG": "karyotype", "VALUE": "46, XY, t(7;12)"}, {"TAG": "BioSampleModel", "VALUE": "Human"}]
Pool_Member_@attributes_sample_title: translocation_HSPC
RUN_SET_RUN_Pool_Member_@attributes_sample_title: translocation_HSPC
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