{"doi":"10.1101/2024.01.06.573649","title":"PHF6 suppresses self-renewal of leukemic stem cells in AML","abstract":"Abstract Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its 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 has context-specific transcriptional effects, skewing the LIC-e transcriptome to a more stem-like state. 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. Overall, our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells. Statement of Significance Leukemia stem cell self-renewal is critical to the pathophysiology of AML. Phf6 deletion accelerates mouse AML by increasing LSC self-renewal, specifically by increasing the fraction of LSC progeny that retain LSC identity. Our work shows how a repressor of HSC self-renewal is inactivated in AML to drive LSC stemness.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489557,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":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":1243671,"name":"Jason Grana","orcid":null,"position":4,"is_corresponding":false},{"id":679943,"name":"Sandeep Gurbuxani","orcid":"0000-0003-0716-8730","position":5,"is_corresponding":false},{"id":636973,"name":"Vikram R. Paralkar","orcid":"0000-0001-6413-951X","position":6,"is_corresponding":false},{"id":1243119,"name":"Sapana Jalnapurkar","orcid":"0000-0003-4416-1941","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","pmid":"38260439","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":[]}