{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["Illumina HiSeq 2000;"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00001001259"],"sample_count":["2"],"description":["EGA dataset EGAD00001001259"],"repository":["EGA"],"title":["RNA-seq of CML074 Tumor tissue; Timpepoint 1"],"pubmed_abstract":["<h4>Background</h4>Chronic myeloid leukaemia (CML) is characterised by the presence of a fusion driver oncogene, BCR-ABL1, which is a constitutive tyrosine kinase. Tyrosine kinase inhibitors (TKIs) are the central treatment strategy for CML patients and have significantly improved survival rates, but the T315I mutation in the kinase domain of BCR-ABL1 confers resistance to all clinically approved TKIs, except ponatinib. However, compound mutations can mediate resistance even to ponatinib and remain a clinical challenge in CML therapy. Here, we investigated a ponatinib-resistant CML patient through whole-genome sequencing (WGS) to identify the cause of resistance and to find alternative therapeutic targets.<h4>Patients and methods</h4>We carried out WGS on a ponatinib-resistant CML patient and demonstrated an effective combination therapy against the primary CML cells derived from this patient in vitro.<h4>Results</h4>Our findings demonstrate the emergence of compound mutations in the BCR-ABL1 kinase domain following ponatinib treatment, and chromosomal structural variation data predicted amplification of BCL2. The primary CD34(+) CML cells from this patient showed increased sensitivity to the combination of ponatinib and ABT-263, a BCL2 inhibitor with a negligible effect against the normal CD34(+) cells.<h4>Conclusion</h4>Our results show the potential of personalised medicine approaches in TKI-resistant CML patients and provide a strategy that could improve clinical outcomes for these patients."],"pubmed_title":["A personalised medicine approach for ponatinib-resistant chronic myeloid leukaemia."],"pubmed_authors":["Korfi K K, Mandal A A, Furney S J SJ, Wiseman D D, Somervaille T C P TCP, Marais R R"],"pubmed_title_synonyms":["leukemia, Specialties, chronic myeloid, Insurance Medicine, insensitive, resistant, Medical Specialty, Iclusig, AP24534, chronic granulocytic leukaemia, chronic, chronic myeloid leukaemia., Medical Specialties, ponatinib hydrochloride, 2-b)pyridazin-3-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-y-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide, Insurance Medicines, Medical Speciality, Speciality, CML, drugs, chronic myelogenous, Medical Specialities, chronic granulocytic leukemia, chronic myelogenous leukemia, medicine, Specialities, chronic myelogenous leukaemia, CML - chronic Myelogenous Leukemia, Myeloid Leukemia, Specialty, Medicine, AP 24534, AP-24534, Medicines, atypical, Insurance, Medical, 3-(2-(imidazo(1"],"name_synonyms":["BcDNA:SD22208, CG4758., CG4918, RplP2, RpA1, p240, sec62, TROVE1, DmelCG4918, RNA-seq, Tp1, RLA2_DROME, RpP1, VAULT2, T1, bs34h02.y1, Tp-1, DmelCG4758, LP2, Whole Transcriptome Shotgun Sequencing, TP1, Dtrp1, rpA1, Stp-1, TLP1"],"pubmed_abstract_synonyms":["Myelocytic, v-abl, Chronic Granulocytic Leukemia, Myeloid, Myelocytic Leukemia, Etiology, Approval, Medical Specialties, Mutations, Alternative, chronic myelogenous, C-abl, Tyrosine-Specific Protein, sequencing assay, Treatment Effect, Method, p150, BCR, symptoms, 10.5, CG40494, JTK7, Protein Kinases, Kinase, Tyrosine-Specific Protein Kinases, 10.9, treatment, average, F, AI325092, Gene Variation, Gene Amplification Abnormality, Abl, Genomes, ABL, V, procedures, BCR-ABL T315I Mutation, AI853148, Transforming Genes, abl, medicine, BCL2 Inhibitor, adult chronic leukemia, Ph1-Positive Myeloid Leukemia, Medicine, Better, ATP Phosphotransferases, close to, screening, sequencing_assay, Followed By, Granulocytic Leukemias, BCR/ABL T315I Mutation, D-Abl, Test, Derived Flag, Procedure, TKI Tyrosine Kinase Inhibitors, predicted, Other Than, Medical Speciality, Approved, BCR/ABL1 T315I Mutation, Tyrosine Specific Protein Kinase, tyrphostins, Combination Therapy, D-abl, Deviation, DmelCG4032, AI561783, Bcl-2, Chronic granulocytic leukemia, VARIATION, 4674, death rate, Tyrosylprotein Kinase, Ph1-Positive Myelogenous, signs, AP24534, Ph1-Positive Myeloid, whole genome, Methodological, Approved Clinical Study Protocol, Approve, ATP:protein-tyrosine O-phosphotransferase, Oncogene, Chromosome, Treatment Outcome, primary tumor, CML - chronic Myelogenous Leukemia, etiology, eve2, CG2328, Myelogenous Leukemias, CLL, Clinical Batch, Proficiency Testing Challenge, In Vitro as Topic, abl1, Effects, Potential, xBcl-2, 5133400C09Rik, number, Iclusig, treatment effect, Therapy Effect, l(3)04674, In Vitro Testing, CML, cAbl, Medical Specialities, Biopolymer Sequencing, Structural, It improved, AP 24534, Variant, atypical, even, Medical, BCR/ABL Fusion Protein with T315I, Technique, In Vitro Tests, DmelCG40494, Approved for EUA, Chronic Granulocytic Leukemias, In, Leukemia, TKI inhibitors, Transforming Gene, Clinical, Supply, dAbl, BCR-ABL1 T315I Mutation, Granulocytic Leukemia, BETTER/IMPROVED/RECOVERING, PHL, Abl1, Structure, Sequencing, Study, increased sensitivity, BCR/ABL1 Fusion Protein with ABL1 NP_005148.2:p.T315I, Combined Treatment, drugs, Supplied, protein tyrosine kinase inhibitors, Ph1-Positive Myelogenous Leukemias, Appearance, Chronic, Tyrosine-Specific, Insurance, AblK, ALL, leukemia, Protein-Tyrosine, Dabl, findings, c-abl, Primary, DAbl, Leukemias, chronic, Cell, Chromosomal, Conclusion, near to, In Vitro Test, chronic myelogenous leukemia, BCR/ABL1 Fusion Protein with NP_005148.2:p.Thr315Ile, Have, Myeloid Leukemias, Amplification, clinical, Eve, EVE, background, Vitro Testing, Except, Xcml, bcr|abl, multimodality treatment, Tyrosine Protein Kinases, Approved for Emergency Use Authorization, Derived Value, 2-b)pyridazin-3-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-y-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide, Causation, D830018M01Rik, Compound, Outcome of Therapy, Primary Cause of Death, chronic myelogenous leukaemia, compound, In Vitro Technique, vicinity of, chronic myeloid leukaemia, D630044D05Rik, Gene Mutation, Strategy, Tyrosylprotein, Chronic Myelocytic Leukemia, Derived, Protein-Tyrosine Kinase, insensitive, Ableson, Chronic Myeloid Leukemia, clinical data, Protein Tyrosine Kinase, Combination, Philadelphia-Positive Myeloid Leukemias, PPP1R50, Driver Device, Multimodal Treatment, Speciality, Techniques, Kinase Inhibitors, Specialities, Tyrosine Kinase Inhibitor, treatment outcome, Mathematical Derivation, Tyrosine-Specific Protein Kinase, Inhibitors, Ph1 Positive, Transforming, Effect, ABT-263, Fusion, BCR1, Chronic Myelocytic Leukemias, Insurance Medicine, DmelCG2328, IMPROVED, Provide, tyrosine kinase inhibitors, Multimodality Therapy, Chronic Myelogenous Leukemias, Myelogenous Leukemia, adult chronic leukaemia, BCR/ABL1 Fusion Protein with NP_005148.2:p.T315I, Granulocytic, Methodological Studies, c-Abl, c-ABL, CG4032, Had, Multimodal Therapy, Subsequent, gene_fusion_variant, disease management, Effective, Therapies, DERIVED, Medicines, Combined Modality Treatment, tyrphostin, Has, BCL-2 Inhibitor, ATP, Gene Mutant, Tyrosine Protein Kinase Inhibitors, Myelogenous, Therapy, Specialties, Primary Tumor, Am ABL, B-cell Lymphoma 2 Inhibitor, Ph1-Positive Myelogenous Leukemia, Philadelphia-Positive, BCR-ABL1 Thr315Ile Mutation, results, CD34, Tyrosine, Ph1-Positive, D22S662, bcl-2, Ph1-Positive Myeloid Leukemias, gene fusion variant, Primary Neoplasm, Philadelphia-Positive Myeloid, Specialty, Tyrosine Specific Protein Kinases, PRCDTH, VI, NOS, D-ash, Clinical Data, AU040960, bcr/abl, Transphosphorylases, Tyrosine Protein Kinase, 20.35, Chronic Granulocytic, Chronic Myelogenous, Derivation, In Vitro, Chronic Myeloid Leukemias, Driver, resistant, Nucleic Acid Sequencing, Tests, conclusion, Multimodality Treatment, Improved, Methodological Study, CG17960, Treatments, Tyrosine Kinase, ABT 263, Insurance Medicines, Dsrc7, chronic granulocytic leukemia, Patient, CHROMOSOME, Gene Variant, Protein Kinase, Sequence Analysis, Provided, 14.10, Dmel_CG00000, Philadelphia Positive, Procedures, Testings, BCR/ABL Thr315Ile Mutation, TKI inhibitor, Gene, hematopoietic progenitor cell antigen CD34, chronic granulocytic leukaemia, presence, Approved Protocol, SEQUENCING, CG17617, Client., Combined Modality Therapy, Therapy Outcome, resistance, Studies, rhoGAP1A, Tyrosine Protein, Philadelphia-Positive Myeloid Leukemia, Next, Phosphotransferase, primary, chronic myeloid, D22S11, Challenge, T315I, EG:23E12.5, Transphosphorylase, BCR/ABL1 Thr315Ile Mutation, EG:23E12.2, ponatinib hydrochloride, Following, time of survival, Clients, BCR-ABL Thr315Ile Mutation, Myeloid Leukemia, Myelocytic Leukemias, AW986256, Gene Amplification, AP-24534, Combined Treatment Modalities, xbcl2, treatment_outcome, Variation, 3-(2-(imidazo(1, E430008G22Rik, Possess, WGS, Molecular Biology, GENETIC_SEQ, ABT263, Medical Specialty, Chronic Myelocytic, Dash, l(3)73Ba, Cause, Client, Phosphotransferases, Testing, count in organism, survival, Chronic myelogenous leukemia, Clinical Lot, DRVFL, CG40453, protein tyrosine kinase inhibitor, In Vitro Testings, techniques, effect, l(3)c-abl, Genes, Chronic Myelogenous Leukemia, high sensitivity toward, Kinases, cml-A, l(2)46Ce, myeloid, patient, C430015F12Rik, BCR/ABL1 Fusion Protein with ABL1 NP_005148.2:p.Thr315Ile, l(2)46Cg, introduction, NUCLEIC ACID SEQUENCING, Ddash/abl, Alternate, l(2)46CFj, l(2)46CFh, chromosome, alternative, Gene Fusion, Protein Tyrosine Kinases, Therapeutic, l(2)46CFp, concurrent therapy, approaches, T315I Mutation, DROTKABL3, DER, Treatment, Gene Amplification Technique, mKIAA3017, c-ABL1, E(eve), BCR/ABL Fusion Protein with Thr315Ile, l(2)46CFg, Chronic Myeloid, methodology"],"description_synonyms":["Desc, Description, Descriptive, Provide., Supplied, Supply, Descriptor, description, Provided, Product Description/Appearance, DESCR"],"additional_accession":[]},"is_claimable":false,"name":"CML074_RNA-seq_TP1 - samples","description":"Description not provided","dates":{"updated":"2017-07-26 15:39:25"},"accession":"EGAD00001001259","cross_references":{"TAXONOMY":["9606"],"pubmed":["25712455"],"EGA":["EGAC00001000095","EGAS00001001150"]}}