{"doi":"10.1038/s41375-024-02142-9","title":"State-transition modeling of blood transcriptome predicts disease evolution and treatment response in chronic myeloid leukemia","abstract":"Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention, before phenotypic changes become detectable.","journal":"Leukemia","year":2024,"id":439670,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8904,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274023,"name":"Russell C. Rockne","orcid":"0000-0002-1557-159X","position":1,"is_corresponding":false},{"id":470208,"name":"Lisa Uechi","orcid":"0000-0001-8215-6938","position":2,"is_corresponding":false},{"id":659036,"name":"Dandan Zhao","orcid":"0000-0001-5194-750X","position":3,"is_corresponding":false},{"id":274022,"name":"Sergio Branciamore","orcid":"0000-0002-2556-8765","position":4,"is_corresponding":false},{"id":428074,"name":"Denis O’Meally","orcid":"0000-0001-7749-9506","position":5,"is_corresponding":false},{"id":553783,"name":"Jihyun Irizarry","orcid":"0000-0003-3967-2288","position":6,"is_corresponding":false},{"id":289773,"name":"Lucy Ghoda","orcid":"0000-0002-8212-3586","position":7,"is_corresponding":false},{"id":235014,"name":"Haris Ali","orcid":"0000-0002-9728-7292","position":8,"is_corresponding":false},{"id":1173755,"name":"Jeffery M. Trent","orcid":null,"position":9,"is_corresponding":false},{"id":249979,"name":"Stephen J. Forman","orcid":"0000-0002-2803-4152","position":10,"is_corresponding":false},{"id":736293,"name":"Yu-Hsuan Fu","orcid":"0000-0002-5917-2961","position":11,"is_corresponding":false},{"id":478530,"name":"Ya‐Huei Kuo","orcid":"0000-0003-2595-0419","position":12,"is_corresponding":false},{"id":230598,"name":"Bin Zhang","orcid":"0000-0003-4703-7524","position":13,"is_corresponding":false},{"id":108574,"name":"Guido Marcucci","orcid":"0000-0002-3983-5908","position":14,"is_corresponding":false},{"id":274018,"name":"David Frankhouser","orcid":"0000-0002-8233-5853","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:00:52.633010Z","pmid":"38307941","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}