---
title: "PHF19 in AML: role in leukemic initiation, prognosis, and survival stratification"
id: "pubmed-42913019"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42913019"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42913019/"
doi: "10.1126/sciadv.aed6757"
published_at: "2026-10-23T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PHF19 in AML: role in leukemic initiation, prognosis, and survival stratification
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42913019
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42913019/)
- **DOI:** [10.1126/sciadv.aed6757](https://doi.org/10.1126%2Fsciadv.aed6757)
- **Published At:** 2026-10-23T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study examined the Polycomb-associated factor **PHF19** (Phf19 in mice) and its effect on acute myeloid leukemia (**AML**) initiation and clinical outcomes. - Investigators deleted Phf19 in hematopoietic cells (Phf19KO) and expressed the oncogenic fusion **MLL-AF9** to model transformation; the source reports integrated multiomic analyses but does not list experimental doses or exact sample sizes. - The Phf19 knockout promoted acquisition of stemlike cellular features in transformed cells, a phenotype the authors linked to impaired hematopoietic stem cell maintenance previously observed in Phf19-deficient mice. - Data indicated that Phf19 loss reduced responsiveness to therapies that induce differentiation in AML models; the abstract does not specify which agents or regimens were tested. - Molecular and functional changes after Phf19 deletion paralleled patterns observed in human AML datasets, according to the authors. - From these comparative analyses, the authors derived a prognostic gene signature named **PHFScore** that stratified patient survival across diverse cellular origins and leukemogenic stages. - The investigators reported that PHFScore revealed previously unrecognized survival-correlating genes; the abstract does not provide the gene list or performance metrics in this summary. - The study links a cell-intrinsic Polycomb factor to both disease initiation and patient prognosis, suggesting **PHF19** modulates transformation biology and therapeutic responsiveness in AML. - The source abstract does not report detailed methodology, numerical survival statistics, cohort sizes, or validation cohorts; those specifics were not included in the provided text.
## Clinical Analysis & Structured Key Points
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Epub 2026 Oct 23. # Polycomb factor PHF19 affects AML initiation, patient prognosis, and survival [Gianni Paolo Gamarra Figueroa](https://pubmed.ncbi.nlm.nih.gov/?term=Gamarra+Figueroa+GP&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Arantxa Gutierrez](https://pubmed.ncbi.nlm.nih.gov/?term=Gutierrez+A&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Enrique Blanco](https://pubmed.ncbi.nlm.nih.gov/?term=Blanco+E&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Pedro Vizán](https://pubmed.ncbi.nlm.nih.gov/?term=Viz%C3%A1n+P&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-2 "Universitat Ramon Llull, Blanquerna School of Health Science, Barcelona 08025, Spain."), [Cecilia Ballaré](https://pubmed.ncbi.nlm.nih.gov/?term=Ballar%C3%A9+C&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Aleksandra Sparavier](https://pubmed.ncbi.nlm.nih.gov/?term=Sparavier+A&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-3 "Centre Nacional d'Anàlisi Genòmica \(CNAG\), Baldiri I Reixac 4, Barcelona 08028, Spain."), [Marta Tosto](https://pubmed.ncbi.nlm.nih.gov/?term=Tosto+M&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Saverio Minucci](https://pubmed.ncbi.nlm.nih.gov/?term=Minucci+S&cauthor_id=42913019)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-4 "Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan 20139, Italy.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-5 "Department of Oncology and Hematology-Oncology, University of Milan, Milan 20122, Italy."), [Lars Velten](https://pubmed.ncbi.nlm.nih.gov/?term=Velten+L&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-6 "Universitat Pompeu Fabra \(UPF\), Barcelona, Spain."), [Luciano Di Croce](https://pubmed.ncbi.nlm.nih.gov/?term=Di+Croce+L&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-6 "Universitat Pompeu Fabra \(UPF\), Barcelona, Spain.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#full-view-affiliation-7 "ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain.") Affiliations Expand ### Affiliations * 1 Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain. * 2 Universitat Ramon Llull, Blanquerna School of Health Science, Barcelona 08025, Spain. * 3 Centre Nacional d'Anàlisi Genòmica (CNAG), Baldiri I Reixac 4, Barcelona 08028, Spain. * 4 Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan 20139, Italy. * 5 Department of Oncology and Hematology-Oncology, University of Milan, Milan 20122, Italy. * 6 Universitat Pompeu Fabra (UPF), Barcelona, Spain. * 7 ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain. * PMID: **42913019** * DOI: [ 10.1126/sciadv.aed6757 ](https://doi.org/10.1126/sciadv.aed6757) Item in Clipboard # Polycomb factor PHF19 affects AML initiation, patient prognosis, and survival Gianni Paolo Gamarra Figueroa et al. Sci Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Sci Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sci+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Sci+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42913019/) . 2026 Oct 23;12(43):eaed6757. doi: 10.1126/sciadv.aed6757. Epub 2026 Oct 23. ### Authors [Gianni Paolo Gamarra Figueroa](https://pubmed.ncbi.nlm.nih.gov/?term=Gamarra+Figueroa+GP&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Arantxa Gutierrez](https://pubmed.ncbi.nlm.nih.gov/?term=Gutierrez+A&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Enrique Blanco](https://pubmed.ncbi.nlm.nih.gov/?term=Blanco+E&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Pedro Vizán](https://pubmed.ncbi.nlm.nih.gov/?term=Viz%C3%A1n+P&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-2 "Universitat Ramon Llull, Blanquerna School of Health Science, Barcelona 08025, Spain."), [Cecilia Ballaré](https://pubmed.ncbi.nlm.nih.gov/?term=Ballar%C3%A9+C&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Aleksandra Sparavier](https://pubmed.ncbi.nlm.nih.gov/?term=Sparavier+A&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-3 "Centre Nacional d'Anàlisi Genòmica \(CNAG\), Baldiri I Reixac 4, Barcelona 08028, Spain."), [Marta Tosto](https://pubmed.ncbi.nlm.nih.gov/?term=Tosto+M&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain."), [Saverio Minucci](https://pubmed.ncbi.nlm.nih.gov/?term=Minucci+S&cauthor_id=42913019)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-4 "Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan 20139, Italy.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-5 "Department of Oncology and Hematology-Oncology, University of Milan, Milan 20122, Italy."), [Lars Velten](https://pubmed.ncbi.nlm.nih.gov/?term=Velten+L&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-6 "Universitat Pompeu Fabra \(UPF\), Barcelona, Spain."), [Luciano Di Croce](https://pubmed.ncbi.nlm.nih.gov/?term=Di+Croce+L&cauthor_id=42913019)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-1 "Centre for Genomic Regulation \(CRG\), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-6 "Universitat Pompeu Fabra \(UPF\), Barcelona, Spain.")[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42913019/#short-view-affiliation-7 "ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain.") ### Affiliations * 1 Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Carrer del Doctor Aiguader 88, Barcelona 08003, Spain. * 2 Universitat Ramon Llull, Blanquerna School of Health Science, Barcelona 08025, Spain. * 3 Centre Nacional d'Anàlisi Genòmica (CNAG), Baldiri I Reixac 4, Barcelona 08028, Spain. * 4 Department of Experimental Oncology, IEO European Institute of Oncology IRCSS, Milan 20139, Italy. * 5 Department of Oncology and Hematology-Oncology, University of Milan, Milan 20122, Italy. * 6 Universitat Pompeu Fabra (UPF), Barcelona, Spain. * 7 ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain. * PMID: **42913019** * DOI: [ 10.1126/sciadv.aed6757 ](https://doi.org/10.1126/sciadv.aed6757) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Acute myeloid leukemia (AML) is marked by unchecked expansion of undifferentiated myeloid cells. Although oncogenic fusions such as MLL-AF9 can initiate disease, the early steps of leukemogenesis and the role of cell-intrinsic regulators remain unclear. We previously showed that the Polycomb-associated factor Phf19 is required for hematopoietic stem cell (HSC) maintenance and state control in mice and that its loss (Phf19KO) impairs HSC function. To define Phf19's role in transformation, we expressed MLL-AF9 in Phf19KO hematopoietic cells and performed integrated multiomic analyses. Phf19 deletion promoted acquisition of stemlike features and reduced responsiveness to differentiation-inducing AML therapies. Molecular and functional consequences of Phf19 loss paralleled those observed in the datasets of patients with AML. From these data, we derived a prognostic signature-PHFScore-which reveals previously unrecognized AML survival-correlating genes that robustly stratify patients across distinct cellular origins and leukemogenic stages, underscoring Phf19's key role in AML biology and prognosis. 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