EGAGenomicsCancer Genomicshttps://ega-archive.org/studies/EGAS00001007167EGAEGA study EGAS00001007167Whole-genome sequencing of BCR-ABL1 lymphoblastic leukemiaRNA-seq of BCR-ABL1 lymphoblastic leukemiarestrictedEGAv-abl, ALL, Dmel_CG00000, Childhood., Dabl, c-abl, Ableson, Lymphocytic Leukemia, abl1, Am ABL, 5133400C09Rik, D-Abl, Dash, l(3)73Ba, Lymphoid Leukemia, Philadelphia-Positive, DAbl, L1 Lymphocytic Leukemia, D22S662, l(3)04674, Lymphoblastic Lymphoma, CML, cAbl, CG17617, C-abl, lymphocytic leukaemia, Acute Lymphoid Leukemia, CG40453, p150, BCR, rhoGAP1A, Acute Lymphocytic, CG40494, JTK7, Acute Lymphoid, D-abl, D-ash, Childhood ALL, DmelCG4032, AI561783, BCR1, DmelCG40494, Lymphoblastic Leukemia, Lymphocytic, bcr/abl, l(3)c-abl, Leukemia, 4674, AI325092, lymphoblastic leukaemia, dAbl, Abl, ABL, D22S11, bcr|abl, Lymphoblastic, PHL, Childhood, Acute Lymphoblastic Leukemia, EG:23E12.5, Abl1, Adult, CG17960, EG:23E12.2, Ddash/abl, AI853148, Dsrc7, L2 Lymphocytic, Acute Lymphoblastic, L1, lymphoblastic leukemia, Acute, L2, L1 Lymphocytic, c-Abl, c-ABL, CG4032, abl, Precursor Cell Lymphoblastic Leukemia Lymphoma, Lymphoma, DROTKABL3, L2 Lymphocytic Leukemia, Lymphoid, mKIAA3017, c-ABL1, Acute Lymphocytic Leukemia, E430008G22Rik, AblKv-abl, B Cells, Ableson, PhrB photolyase activity, Bursa-Dependent Lymphocytes, B cell, pigmented epithelium, prevention, Mutations, C-abl, Kinase Inhibitors, Tyrosine Kinase Inhibitor, responsivity, p150, BCR, Mother Cells, CG40494, Inhibitors, 3, JTK7, Kinase, NUP96, prevention and control, epithelium, BCR1, treatment, AI325092, reference sample, Abl, ABL, tyrosine kinase inhibitors, pigmented retina, Leucocythemias, Adult, DNA cyclobutane dipyrimidine photolyase activity, SUPPRESSOR OF AUXIN RESISTANCE 3, preventive measures, AI853148, reaction, Acute Lymphoblastic, B lymphocyte, c-Abl, c-ABL, CG4032, abl, Precursor Cell Lymphoblastic Leukemia Lymphoma, disease management, Therapies, Lymphoid, stage, ATP Phosphotransferases, tyrphostin, ATP, Tyrosine Protein Kinase Inhibitors, Therapy, PRE, preventive therapy, B Lymphocytes, Am ABL, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, D-Abl, Philadelphia-Positive, TKI Tyrosine Kinase Inhibitors, Tyrosine, D22S662, Colony-Forming Unit, lymphocytic leukaemia, retinal pigment, Stem Cell, Acute Lymphoid Leukemia, dipyrimidine photolyase (photosensitive), Acute Lymphocytic, tyrphostins, D-abl, D-ash, retinal pigment layer, DmelCG4032, AI561783, Lymphoblastic Leukemia, Mother Cell, bcr/abl, Transphosphorylases, Leucocythemia, absence, 4674, Stem, Colony Forming Units, Acute Lymphoblastic Leukemia, CG17960, Treatments, Tyrosine Kinase, Phenotypes, Dsrc7, phr A photolyase activity, DNA-photoreactivating enzyme, Patient, B-Lymphocyte, Lymphoma, Cells, L2 Lymphocytic Leukemia, Acute Lymphocytic Leukemia, Dmel_CG00000, Lymphocytic Leukemia, abl1, developmental stage, Colony-Forming Units, 5133400C09Rik, TKI inhibitor, Progenitor Cell, photoreactivating enzyme activity, l(3)04674, CML, cAbl, CG17617, leukaemia NOS, rhoGAP1A, Leucocythaemias., stratum pigmentosa retinae, Leucocythaemia, leukaemia, Childhood ALL, Phosphotransferase, Progenitor, DmelCG40494, Lymphocytic, reactivity, B-cell, Leukemia, MOS3, TKI inhibitors, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, lymphoblastic leukaemia, dAbl, PRECOCIOUS, D22S11, absent from organism, F23A5.3, Mother, PHL, EG:23E12.5, Transphosphorylase, Abl1, EG:23E12.2, L2 Lymphocytic, L1, lymphoblastic leukemia, L2, L1 Lymphocytic, protein tyrosine kinase inhibitors, Clients, heterogeneity, F23A5_3, Controlled, E430008G22Rik, AblK, ALL, leukemia, Controlling, Colony Forming Unit, Dabl, c-abl, Progenitor Cells, Dash, l(3)73Ba, Lymphoid Leukemia, DAbl, L1 Lymphocytic Leukemia, Client, Phosphotransferases, Leukemias, Cell, Lymphoblastic Lymphoma, MODIFIER OF SNC1, CG40453, deoxyribonucleic photolyase activity, protein tyrosine kinase inhibitor, Acute Lymphoid, Leucocythaemias, l(3)c-abl, RPE, photolyase activity, Kinases, prophylaxis, bcr|abl, Lymphoblastic, Bursa-Equivalent Lymphocyte, patient, Childhood, Ddash/abl, p. pigmentosa retinae, Acute, Therapeutic, control, DROTKABL3, Treatment, deoxyribonucleate pyrimidine dimer lyase (photosensitive), response, mKIAA3017, c-ABL1, B-lymphocytefalseTranscriptomic classes of BCR-ABL1 lymphoblastic leukemiaIn BCR-ABL1 lymphoblastic leukemia, treatment heterogeneity to tyrosine kinase inhibitors (TKIs), especially in the absence of kinase domain mutations in BCR-ABL1, is poorly understood. Through deep molecular profiling, we uncovered three transcriptomic subtypes of BCR-ABL1 lymphoblastic leukemia, each representing a maturation arrest at a stage of B-cell progenitor differentiation. An earlier arrest was associated with lineage promiscuity, treatment refractoriness, and poor patient outcomes. A later arrest was associated with lineage fidelity, deep and durable leukemia remissions, and improved patient outcomes. Each maturation arrest was marked by specific genomic events that control different transition points in B-cell development. Interestingly, these events were absent in BCR-ABL1+ pre-leukemic stem cells isolated from patients regardless of subtype, which supports that transcriptomic phenotypes are determined downstream of the leukemia-initialing event. Overall, our data indicate that treatment response and TKI-efficacy is an unexpected outcome of the differentiation stage at which this leukemia transforms.2023-06-07 09:29:21EGAS000010071679606EGAD00001010323EGAD00001010307EGAC00001000591