ArticleScience translational medicine2024
BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML.
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Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed.
- Review
- Epigenetic activation of NK-cell effector programs and caspase-8-dependent apoptosis mediates the antitumor activity of LGP in NSCLC.Journal of ginseng research · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Enhanced ITGA3 expression induced by helicobacter pylori infection facilitates gastric cancer progression via NF-κB and Smad4.Molecular and cellular biochemistry · 2026Article
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Defining the role of natural killer cells in acute myeloid leukemia through the lens of single-cell omics.Frontiers in immunology · 2026Review
- Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency.Cancer cell · 2025Article
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Therapeutic hurdles in acute myeloid leukemia: Leukemic stem cells, inflammation and immune dysfunction.Current opinion in pharmacology · 2025Review
- Overexpressing natural killer group 2 member A drives natural killer cell exhaustion in relapsed acute myeloid leukemia.Signal transduction and targeted therapy · 2025Article
- Robust differentiation of NK cells from MSLN.CAR-IL-15-engineered human iPSCs with enhanced antitumor efficacy against solid tumors.Science advances · 2025Article
- Natural killer cells' functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes.Nature communications · 2025Article
- Key Genes Associated With Functional Specialization of Neonatal Peripheral Monocytes.Human mutation · 2025Article
- Construction of a novel inflammatory-related prognostic signature of acute myelocytic leukemia based on conjoint analysis of single-cell and bulk RNA sequencing.Frontiers in immunology · 2025Article
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Authors and funding
50 authors.
Bijender KumarDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-7835-3875
Anand SinghDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-6855-3352
Rafet BasarDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-4713-0454
Nadima UpretyDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-4379-6208
Ye LiDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-7727-0875
Huihui FanDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.ORCID 0000-0003-4233-5389
Ana Karen Nunez CortesDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-5380-9274
Mecit KaplanDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-0079-8617
Sunil AcharyaDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3907-9321
Hila ShaimDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anna C XuDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-6648-4130
Manrong WuDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-5691-6929
Emily EnsleyDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Dexing FangDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0009-0003-9328-1250
Pinaki P BanerjeeDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Luciana Melo GarciaDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Silvia TibertiDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2141-2365
Paul LinDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-0524-267X
Hind RafeiDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-5724-4183
Maliha Nuzhat MunirDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0009-0004-4737-3725
Madison MooreDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0009-0009-1814-1905
Mayra ShanleyDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-3739-0287
Mayela MendtDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lucila N KerbauyDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bin LiuDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Alexander BiederstädtDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2805-8231
Elif GokdemirDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Susmita GhoshDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-6591-9147
Kiran KunduDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-7586-4696
Francia Reyes-SilvaDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0009-0001-5396-7691
Xin Ru JiangDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xinhai WanDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
April L GilbertDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-8626-1919
Merve DedeDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-0868-5863
Vakul MohantyDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-5536-6750
Jinzhuang DouDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-0090-4264
Patrick ZhangDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Enli LiuDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Luis Muniz-FelicianoDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gary M DeyterDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2638-0825
Abhinav K JainDepartment of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-3268-514X
Juan Jose Rodriguez-SevillaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4741-7925
Simona CollaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Guillermo Garcia-ManeroDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3631-2482
Elizabeth J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-3947-4126
Ken ChenDepartment of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-4013-5279
Hussein A AbbasDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2946-3562
Kunal RaiDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-2321-6894
Katayoun RezvaniDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-9599-2246
May DaherDepartment of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-6026-8397
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MUniversity of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI REZVANI, KATY · 2003 to 2023
$43.7MNext Generation Engineered NK Cells for Lymphoma Patients after CD19 CAR-T Cell Failure.R01CA280827 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Rafet Basar, May Daher · 2023 to 2026
$1.5MNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632NCI NIH HHS R01 CA280827
Abstract
Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ-integrin/TGF-β/SMAD pathway but, once established, was persistent because of profound epigenetic reprogramming. We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. Mechanistically, we found that BATF was directly regulated and induced by SMAD2/3 and, in turn, bound to key genes related to NK cell exhaustion, such as
Indexed as
Basic-Leucine Zipper Transcription FactorsEpigenesis, GeneticKiller Cells, NaturalLeukemia, Myeloid, AcuteAnimalsCellular ReprogrammingHumansMiceSignal TransductionSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaBasic-Leucine Zipper Transcription FactorsBATF protein, humanSmad2 ProteinSmad3 ProteinTransforming Growth Factor beta
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.