{"doi":"10.1038/s41375-024-02340-5","title":"PHF6 suppresses self-renewal of leukemic stem cells in AML","abstract":"Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors accompanied by a differentiation arrest. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its isolated loss increases mouse HSC self-renewal without malignant transformation. We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells. We define the in vivo hierarchy of Hoxa9-driven AML and identify a population that we term the \"LIC-e\" (leukemia initiating cells enriched) population. We find that Phf6 loss expands the LIC-e population and skews its transcriptome to a more stem-like state; concordant transcriptome shifts are also observed on PHF6 knockout in a human AML cell line and in PHF6 mutant patient samples from the BEAT AML dataset. We demonstrate that LIC-e accumulation in Phf6 knockout AML occurs not due to effects on cell cycle or apoptosis, but due to an increase in the fraction of its progeny that retain LIC-e identity. Our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells.","journal":"Leukemia","year":2024,"id":435530,"datarank":0.535879147401537,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.15113674378230635,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.15113674378230635,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":10,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE270756"]},"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":1243120,"name":"Aishwarya Pawar","orcid":"0000-0002-1644-1201","position":1,"is_corresponding":false},{"id":853129,"name":"Subin S. George","orcid":"0000-0002-3452-0528","position":2,"is_corresponding":false},{"id":636970,"name":"Charles Antony","orcid":"0000-0003-3574-4184","position":3,"is_corresponding":false},{"id":889117,"name":"Patrick Somers","orcid":"0000-0002-5932-9236","position":4,"is_corresponding":false},{"id":1243671,"name":"Jason Grana","orcid":null,"position":5,"is_corresponding":false},{"id":1243672,"name":"Victoria K. Feist","orcid":null,"position":6,"is_corresponding":false},{"id":679943,"name":"Sandeep Gurbuxani","orcid":"0000-0003-0716-8730","position":7,"is_corresponding":false},{"id":636973,"name":"Vikram R. Paralkar","orcid":"0000-0001-6413-951X","position":8,"is_corresponding":false},{"id":1243119,"name":"Sapana Jalnapurkar","orcid":"0000-0003-4416-1941","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:00:08.103086Z","pmid":"39004675","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":[]}