{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["RNASeq"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001005819"],"host":["EGA"],"description":["EGA study EGAS00001005819"],"dataset_title":["Acute myeloid leukemia bulk RNA-seq (Diagnosis and Relapse)"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["Myelogenous Leukemias, Myelocytic, Acute Myeloblastic, acute myeloblastic leukemia, d230, Nonlymphocytic Leukemia, acute non lymphoblastic leukemia, Myeloid, acute myeloblastic leukaemia, acute myelogenous leukaemia, Myelocytic Leukemia, Gene, dTAFII250, EfW1, Acute Myeloid, Gene Expression Profilings, Acute Myelocytic Leukemias, dmTAF[[II]]230, Transcript Expression Analysis, mRNA Differential Displays, Gene Expression Pattern Analysis, acute non lymphoblastic leukaemia, dmTAF1, Taf230, M1., Gene Expression Monitorings, Acute Myelocytic, Acute Nonlymphoblastic, Relapses, acute myeloid, Analysis, Profilings, Myeloblastic Leukemia, TAF250, Taf200, Leukemia, dTAF[[II]]250, TFIID TAF250, Analyses, cel, cell, Recrudescences, Acute Myelogenous, Acute Myeloblastic Leukemia, Recurrences, Taf1p, Transcriptomics, Myelogenous Leukemia, Acute Nonlymphocytic Leukemias, Transcript Expression, Transcriptome Analysis, Monitoring, Acute Myeloid Leukemia without Maturation, dTAF250, Gene Expression Analysis, Acute Nonlymphoblastic Leukemia, Acute Nonlymphocytic Leukemia, Myeloid Leukemia, Myelocytic Leukemias, ANLL, Nonlymphoblastic Leukemias, TAF, Expression Analyses, acute myelogenous, leukemia, Myelogenous, Relapse, SINGLE, Profiling, M1, dTAF[[II]]230, TAF[[II]]250, M2, Transcriptome, acute myelogenous leukemia, TAF200, Monitorings, l(3)84Ab, BG:DS00004.13, TAFII-250, TAF250/230, Cell, Leukemias, dTAF230, AML, Acute Myelocytic Leukemia, Nonlymphoblastic Leukemia, Gene Expression, Differential Display, Nonlymphocytic Leukemias, TAFII250, Nonlymphoblastic, Transcript Expression Analyses, Acute Myeloid Leukemias, Recrudescence, p230, Myeloid Leukemias, TAF[[II]]250/230, TFIID, Acute Nonlymphocytic, mRNA Differential Display, Acute Myelogenous Leukemia, Taf[[II]]250, acute, Acute myelogenous leukemia, Single Person, Gene Expression Monitoring, TAF[[II]]230, Transcriptome Profiling, distinct, mRNA, Myeloblastic, Transcriptome Profilings, susceptibility to, Myeloblastic Leukemias, Acute Myeloid Leukemia, acute myeloid leukemia, acute myeloid leukaemia, TAF[II]250, Differential Displays, CG17603, Nonlymphocytic, TAF[[II]], Transcriptome Analyses, Acute Myeloid Leukemia with Maturation, DmelCG17603, Acute, Gene Expression Analyses, Only, Taf250, Acute Nonlymphoblastic Leukemias, SR3-5, Acute Myeloblastic Leukemias, Acute Myelogenous Leukemias, Solitary, Expression Analysis, Single, AML - acute Myeloid Leukemia, Alone, TAF230, TAF1"],"description_synonyms":["hematopoietic neoplasm, hematopoietic precursor cell, Ribonucleic, Similarity, DRI Intermediate Risk, \"blood cancer\" EXACT [CSP2005:2004-0139], CG33956, 2610315D21Rik, Materials, \"hematopoietic tumors\" EXACT [NCI2004_11_17:C27134], acute non lymphoblastic leukemia, Myeloid, IPI High Risk, hemopoietic stem cell, CDR, Stem Cells, Suggestion, High Risk, D-fos, gamma-Ada, jra, Tumor, Diagnosis, Single Cell Specimen, DmTOR, dmTAF[[II]]230, Alternative, Enhancer-Binding Protein, Likely, Accepted, symptoms, Employed, Scanning Transmission Electron Microscopy, Related, Whole Transcriptome, Transcriptome Sequencing, RAFT1, Mammalian target of rapamycin, Consortium, Contains, primary stem, Non Polyadenylated, Monoclonal Cellular Population Present, treatment, Centers, Transcriptional, Junc, organa haemopoietica, TFIID TAF250, Gene Variation, haematopoietic cancer, haemopoietic system, cel, Cell Locomotion, V, Evolution, amlcr1, blood cancer, malignant hematopoietic neoplasm, Jun, JUN, Monotypic Cells Present, blutbildende Stammzelle, Network Interface, D-Fos, any therapy, Relationship, Diagnose, single organism signaling, acute myelogenous, Tumors, Therapeutic Procedure, Clonality, screening, jun, EG:198A6.2, dTAF[[II]]230, t(8, \"Hematological tumors\" EXACT [NCI2004_11_17:C27134], plomo, FLT3-ITD Activating Mutation, D-Jun, AML1/ETO Fusion Gene, Exome, DRI High Risk, familial, TAF200, plomb, HSC, MTG8, Clonal Cellular Population Present, Diagnoses, Poorly marginated, Activating FLT3-ITD Mutation, Benign, Postmortem, Hematopoietic Stem, Recrudescence, FOS, Fos, D-jun, Hematopoietic Malignancies, Diverse, Ribonucleic acids, malignant haematopoietic neoplasm (morphologic abnormality), Regulated, evi-1, Adapt, ASC-T3, High risk, Acid, Hematopoietic, Complete Transcriptome, AML1-MTG8, L'sc, Myeloblastic, fos, Definite Attribution, High Risk (MRD > 0.05%), AP1gamma1, Rapamycin and FKBP12 target 1, IPI Low High Group, signs, Acute Myeloid Leukemia, Benign Neoplasms, Employment, Hematologic Malignancies, Leading, Malignant Neoplasms, Hematopoietic Systems, G0S3, primary axis, Taf250, Material, hemopoietic tissue, IPSS-R High Risk, Cells, Whole Exome Sequencing, Fra, \"Hematologic malignancy\" EXACT [SNOMEDCT_2005_07_31:269475001], clone, other neoplasm, l'sc, sc/T3, TAF230, Hematopoietic Colony-Forming Units, transcription, GOS3, Activator Protein 1, \"hematopoietic cancer\" EXACT [], Neoplasms, cJun, fra, stalk, DmelCG33956, Sharing, GOSB, Transcription Factor AP 1, ascT3, Therapeutic Technique, AML/ETO Fusion Gene, Hematopoietic Malignancy, L'Sc, hematopoietic progenitor cell, hematolymphoid system, Gene Products, Screening, TOR, Antemortem, dJRA, dJra, NCI Consortium or Network, acute myeloid leukaemia (AML), Greater than 5.0, Modification, Transcription, Complete, Leukemia, RNA Expression, Exome Sequencings, dTAF[[II]]250, Bx34, Recrudescences, cell, Profile, absent from organism, IPSS-R Intermediate Risk, High Risk Acute Leukemia, dJun, dJUN, Genetic Transcription, tor, Tpr, TPR, Hematopoietic Neoplasms, Diagnoses and Examinations, Recurrences., pebp2ab, culm, Sequencing, FLT3 ITD, Neoplasias, dTAF250, DmelCG2275, Movement, Whole Exome, synopsis, Monotypic Cell Population Present, Whole, l(2R)IA109, \"hematopoietic neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:414388001], constitutitional genetic, Frap1, Cancer, leukemia, ETO, Antemortem Diagnoses, SINGLE, Probably, RNA, Adapted, findings, Malignant Neoplasm, Complete Exome Sequencings, FLT3/ITD Mutation, Unit, Progenitor Cells, Preceding, c-jun, RNS, FRAP1, BG:DS00004.13, FRAP2, HIGH RISK, mTOR, administration (substance), Cell, Djun, dTAF230, AML1-ETO, AML, Exome Sequencing, dm-Jun, MT, Neoplasm, djun, TAF[[II]]250/230, Revised International Prognostic Scoring System for Myelodysplastic Syndrome Intermediate Risk Category, AI462102, aml1-evi-1, colony forming unit hematopoietic, IPSS-R Risk Category High, dgamma, DJUN, DJun, Before, Taf[[II]]250, aml, Kay, Definitely Related to Intervention, Single Person, Modified, AML1-EVI-1, primary cancer, \"hematopoietic and lymphoid system tumor\" EXACT [], Treated, Similar, c-Fos, dfos, Therapeutic Method, 21), Blood Cancer, Likeliness, Containing, HSC cell, CG2275, Cancers, CBFA2, Ribonucleic Acid, Changed, bHLHc28, Hematopoietic Stem Cell, FRAP, malignant tumor, hematologic malignancy, FLT3 Internal Tandem Duplication, signalling, Blutbildungssystem, High, AP1, Acute, CT16317, Monotypic, dAP-1, dFos, signalling process, c-fos, Specific, Hematological, MTOR, Solitary, SUB1.5, Gene Mutation, DFos, DFOS, hereditary, Neoplasia, Alone, colony forming unit spleen, Extensive, Networks, author summary, Antemortem Diagnosis, D-jun/Jra, P115-RHOGEF, TREATMENT, treatment_or_therapy, ZMYND2, AP-1, d-jun, Blood, FKBP12-rapamycin complex-associated protein, Single-cells, Pb, l(2)k03905, \"Hematologic neoplasm (disorder)\" EXACT [SNOMEDCT_2005_07_31:129154003], BLAST, hematopoietic tissue, relapse, Cbfa2, Dfos, GEF1, Clonal, DFra, Mother Cells, Relapses, Prior, Cell Motility, hematopoietic tumors, Hematopoietic Colony-Forming Unit, RNA Gene Products, hematological system, Definite, L(1)sc, dFra, dFRA, CG15507, CG15509, Pebp2a2, malignant hematopoietic neoplasm (morphologic abnormality), CFU-S, RUNX1-RUNX1T1 Fusion Gene, Complete Exome Sequencing, Acute Myeloblastic Leukemia, Recurrences, Whole Transcriptome Sequencing, l(2)IA109, Association, treatment or therapy, Comprise, aml1, dtor, Hematopoietic Progenitor Cells, T3, genetic, XAML, AS-T3, Gene Transcription, Movements, Disease Risk Index High Risk, malignant neoplasm, signaling process, disease management, Therapies, c-Jun, Locomotion, ANLL, Malignancies, Hematologic malignancy, AP-1[gamma], FLT3-ITD, d-fos, associated, hemopoietic system, Biomaterial Treatment, Intermediate Risk, dTOR, dTor, gamma, FK506-binding protein 12-rapamycin complex-associated protein 1, Gene Mutant, Hematopoietic Progenitor Cell, Therapy, Pre, Relapse, Mechanistic target of rapamycin, Motility, TX, CBF-alpha-2, administration, ETO/AML Fusion Gene, d-JRA, AML-ETO Fusion Gene, and Consortia, ribose nucleic acid, Aml1, AML1, AP1gamma, Cell Migration, ribonucleic acids, Blei, Therapy Trial, RNA-seq, 82Pb, TAFII-250, Single Cell, TAF250/230, Activator Protein-1, results, AP 1 Enhancer Binding Protein, Contained, Electron Microscopy, LSC cell, Revised International Prognostic Scoring System for Myelodysplastic Syndrome High Risk Category, TAFII250, Screenings, AS-C T3, Colony-Forming Unit, EVI-1, PEBP2aB, Stem Cell, Examinations and Diagnoses, Ribonukleinsaeure, CBFA2T1, pentosenucleic acids, Genetic Materials, Adverse Event Definitely Related to Intervention, Adverse Event Related to Intervention, Postmortem Diagnosis, Genetic Material, RAPT1, Mother Cell, Treatment Study, Diagnoses and Examination, Acute myelogenous leukemia, \"Hematologic malignancy (disorder)\" EXACT [SNOMEDCT_2005_07_31:127221002], Postmortem Diagnoses, absence, D-fos/kay, Hematopoietic Progenitor, Stem, System, susceptibility to, Heterogeneity, Network Device, Colony Forming Units, ACC/AHA Lesion Complexity Score C, CG17603, TAF[[II]], Treatments, Clone, summary, acute myeloid leukemia (AML), Patient, hematologic cancer, SR3-5, d-Jun, 5092, aml-1, l[1]sc, STEM, Hematologic Neoplasm, Cistron, Gene Variant, inherited genetic, Treatment Epoch, Hematologic neoplasm, Transcriptome Sequencings, Regulation, d230, biological signaling, Migration, Activating FLT3-ITD Gene Mutation, Complete Exome, DmelCG3839, CG5092, Colony-Forming Units, Consortium or Network, Progenitor Cell, Benign Neoplasm, p55, l(2)46Ef, clonality, Gene, dTAFII250, Network, Established, Malignant, EfW1, l(2)k17004, Hematopoietic Neoplasm, Blasts, blood forming stem cell, acute non lymphoblastic leukaemia, dmTAF1, Relations, Taf230, cg9113, Genetic heterogeneity, Blood Cancers, resistance, Treat, Mass, International Prognostic Index High Risk Group, American College of Cardiology/American Heart Association Lesion Complexity Score C, hematopoietic cancer, Whole Transcriptome Shotgun Sequencing, acute myeloid, AP-1 Enhancer-Binding Protein, Therapeutic Interventions, Progenitor, Hematological Malignancy, TREAT, TAF250, fbz, DmelCG8274, RUNX1/RUNX1T1 Fusion Gene, Runx-1, study, Somatic, WES, Taf200, Diversity, Genetic, AMLCR1, Malignancy, dlhD, Suggest, Poorly Marginated Nodule, haematopoietic system, Mother, l(1)1Ba, Taf1p, flat, DmelCG9113, Contain, Cbfa2t1h, Cell Movements, Non-Polyadenylated RNA, l-sc, Administration, Hematological Neoplasms, Hematologic Malignancy, Pebpa2b, Clients, heterogeneity, lead, ACC/AHA LESION COMPLEXITY SCORE C, Cbfa2t1, TAF, CT24817, Share, Hematological Malignancies, data, GENETIC_SEQ, Colony Forming Unit, TAF[[II]]250, axis, INTERMEDIATE RISK, Hematologic, Like, l(3)84Ab, FLT3-ITD Mutation, Intermediate, Certain, Scanning Transmission, FRAP/TOR, Hematological Neoplasm, Poorly, Cistrons, DmelCG5092, Related Attribution, Client, Somatic Evolution, Examination and Diagnoses, Lsc, LSC, 2.7.11.1, hemopoietic progenitor cell, Mass Screenings, p230, yeast nucleic acid, Units, TFIID, cbfa2, High Risk of Toxic Accumulation, AML1/MTG8, CG3839, any_therapy, lsc, Gain, Disease Risk Index Intermediate Risk, haematological system, ribonucleic acid, Hematopoietic Colony-Forming, hematopoietic and lymphoid system tumor, Complete Transcriptome Sequencing, TAF[[II]]230, CG9113, distinct, Hematological tumors, Xaml1, Non Polyadenylated RNA, Lbcl2, plumbum, Non-Polyadenylated, IPSS-R Risk Category Intermediate, malignant haematopoietic neoplasm, CT24745, haematopoietic tissue, Rapamycin target protein 1, patient, TAF[II]250, AI327068, Alternate, Specified, AML1T1, C-FOS, therapy, DmelCG17603, alternative, Only, AP-1 Enhancer Binding Protein, Therapeutic, Change, CG8274, progenitor cell, Drug Accumulation Greater than 5, BEFORE, Treatment, Single, JRA, \"malignant hematopoietic neoplasm (morphologic abnormality)\" EXACT [SNOMEDCT_2005_07_31:414644002], LBcl2, LBCL2, TAF1"],"additional_accession":[]},"is_claimable":false,"name":"Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia","description":"Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. To gain insight into the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs, we employed whole exome sequencing and single-cell RNA-seq to longitudinally profile two t(8;21) (AML1-ETO = RUNX1-RUNX1T1), and four FLT3-ITD AML cases. \nThe single cell RNA data underpinned the tumor heterogeneity amongst patient blasts. The Dx-Re transcriptomes of high risk FLT3-ITD pairs formed a continuum from extensively changed in the absence of significantly mutational changes in AML-associated genes to rather similar Dx-Re pair of an intermediate risk FLT3-ITD. In one high risk FLT3-ITD pair, a pathway switched from an AP-1 regulated network in Dx to mTOR signaling in Re. The distinct Dx-Re AML1-ETO pairs comprise clusters that share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells probably evolved from the Dx LSC-like cells. \nIn summary, our study revealed a continuum from drastic transcriptional changes to extensive similarities between respective Dx-Re pairs that are poorly explained by the well-established model of clonal evolution. Our results suggest alternative and currently unappreciated and unexplored mechanisms that lead to therapeutic resistance and AML recurrence.","dates":{"updated":"2022-03-09 13:25:18"},"accession":"EGAS00001005819","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001008374","EGAC00001002425"]}}