{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:52:48Z","timestamp":1791373968498,"version":"4.3.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Genomic instability and immune escape are linked features of hematologic malignancies, but the mechanisms that allow malignant cells to tolerate persistent nuclear and genotoxic stress while avoiding damaging DNA-sensing responses remain incompletely defined. Barrier-to-autointegration factor 1 (BANF1) is a small DNA-binding protein that bridges chromatin, couples it to nuclear-envelope proteins, supports postmitotic nuclear assembly and rupture repair, modulates several DNA-damage-response pathways, and restricts productive engagement of cyclic GMP-AMP synthase (cGAS) with self-DNA. Human BANF1 variants associated with progeroid disease and motor neuronopathy, together with functional studies in solid tumors, establish organism-level and cancer relevance, but they do not establish a selective blood-cancer dependency. Here, we integrate direct BANF1 evidence with disease-specific studies of replication stress, repair dependence, and innate DNA sensing in acute myeloid leukemia, T-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, multiple myeloma, myelodysplastic syndromes, and virus-associated lymphoid malignancies. The evidence supports a focused question: whether defined malignant hematopoietic states require BANF1 more than normal hematopoiesis, and which BANF1 function accounts for that difference. Direct hematologic evidence remains concentrated in gammaherpesvirus-associated models and concerns viral reactivation and innate signaling rather than a demonstrated lymphoma-survival dependency. We therefore distinguish direct perturbation evidence from related disease biology and from mechanistic hypotheses, emphasize that repair regulation is context dependent and that cGAS recruitment is not equivalent to cGAMP production, and critically assess survival evidence, pharmacologic tractability, and normal-cell safety. BANF1 therefore remains a mechanistically compelling candidate for disease-specific investigation in hematologic malignancies, with selectivity, signaling context, and normal-cell safety unresolved.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1990375","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:14:53Z","timestamp":1791371693000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BANF1 at the crossroads of genome stability and innate immunity: emerging implications for hematologic malignancies"],"prefix":"10.3389","volume":"17","author":[{"given":"Xia","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Hematology, The Affiliated People\u2019s Hospital of Ningbo University","place":["Ningbo, China"]},{"name":"Institute of Hematology, Ningbo University","place":["Ningbo, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Affiliated People\u2019s Hospital of Ningbo University","place":["Ningbo, China"]},{"name":"Institute of Hematology, Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Affiliated People\u2019s Hospital of Ningbo University","place":["Ningbo, China"]},{"name":"Institute of Hematology, Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhi","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Affiliated People\u2019s Hospital of Ningbo University","place":["Ningbo, China"]},{"name":"Institute of Hematology, Ningbo University","place":["Ningbo, 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