Mikko Purhonen, Mikael Tatun, Katariina Luukkainen, Kevin Hung, Henri Sundquist, Oda Tafjord, Stina Söderlund, Shady Adnan-Awad, Anni Dohlen, Johanna Heikkinen, Perttu Koskenvesa, Sanna Siitonen, Satu Mustjoki, Naranie Shanmuganathan, Coral Bryce, Signe Danielsson, Henrik Hjorth-Hansen, Ulla Olsson-Strömberg, Takashi Kumagai, Shinya Kimura, David M. Ross, Oscar Brück
{"title":"诊断时的粒细胞丰度和成熟状态预测CML的无治疗缓解","authors":"Mikko Purhonen, Mikael Tatun, Katariina Luukkainen, Kevin Hung, Henri Sundquist, Oda Tafjord, Stina Söderlund, Shady Adnan-Awad, Anni Dohlen, Johanna Heikkinen, Perttu Koskenvesa, Sanna Siitonen, Satu Mustjoki, Naranie Shanmuganathan, Coral Bryce, Signe Danielsson, Henrik Hjorth-Hansen, Ulla Olsson-Strömberg, Takashi Kumagai, Shinya Kimura, David M. Ross, Oscar Brück","doi":"10.1038/s41375-025-02769-2","DOIUrl":null,"url":null,"abstract":"<p>Treatment-free remission (TFR) has become a therapeutic objective for selected chronic-phase chronic myeloid leukemia (CP CML). However, no standardized biomarker is yet in clinical use. In this multi-center study, we explored the potential of bone marrow (BM) cytomorphology given its global accessibility and integral role in clinical diagnostics. We included diagnostic BM aspirate samples of 113 CP CML patients from seven clinical sites having attempted first TKI discontinuation. We digitized cytomorphological slides into 100x-magnified high-resolution images and analyzed these with deep learning-based image analysis. We profiled the BM cytomorphological fingerprint of CP CML patients and recapitulated the known granulocytic predominance and reduction of lymphoid, monocytic and erythroid cells in comparison to an extensive cohort of 942 control BM samples. We discovered neutrophil abundance and granulocytic maturation to associate with sustained TFR. We confirmed these visually and demonstrated their independent impact over known clinical factors. Our study underlines the potential of computational BM cytomorphology to identify novel clinical biomarkers and suggests that granulocytic expansion and maturation at diagnosis could reflect intrinsic disease pathology influencing TFR maintenance.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"36 1","pages":""},"PeriodicalIF":13.4000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML\",\"authors\":\"Mikko Purhonen, Mikael Tatun, Katariina Luukkainen, Kevin Hung, Henri Sundquist, Oda Tafjord, Stina Söderlund, Shady Adnan-Awad, Anni Dohlen, Johanna Heikkinen, Perttu Koskenvesa, Sanna Siitonen, Satu Mustjoki, Naranie Shanmuganathan, Coral Bryce, Signe Danielsson, Henrik Hjorth-Hansen, Ulla Olsson-Strömberg, Takashi Kumagai, Shinya Kimura, David M. 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We discovered neutrophil abundance and granulocytic maturation to associate with sustained TFR. We confirmed these visually and demonstrated their independent impact over known clinical factors. Our study underlines the potential of computational BM cytomorphology to identify novel clinical biomarkers and suggests that granulocytic expansion and maturation at diagnosis could reflect intrinsic disease pathology influencing TFR maintenance.</p>\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":\"36 1\",\"pages\":\"\"},\"PeriodicalIF\":13.4000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41375-025-02769-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41375-025-02769-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML
Treatment-free remission (TFR) has become a therapeutic objective for selected chronic-phase chronic myeloid leukemia (CP CML). However, no standardized biomarker is yet in clinical use. In this multi-center study, we explored the potential of bone marrow (BM) cytomorphology given its global accessibility and integral role in clinical diagnostics. We included diagnostic BM aspirate samples of 113 CP CML patients from seven clinical sites having attempted first TKI discontinuation. We digitized cytomorphological slides into 100x-magnified high-resolution images and analyzed these with deep learning-based image analysis. We profiled the BM cytomorphological fingerprint of CP CML patients and recapitulated the known granulocytic predominance and reduction of lymphoid, monocytic and erythroid cells in comparison to an extensive cohort of 942 control BM samples. We discovered neutrophil abundance and granulocytic maturation to associate with sustained TFR. We confirmed these visually and demonstrated their independent impact over known clinical factors. Our study underlines the potential of computational BM cytomorphology to identify novel clinical biomarkers and suggests that granulocytic expansion and maturation at diagnosis could reflect intrinsic disease pathology influencing TFR maintenance.
期刊介绍:
Title: Leukemia
Journal Overview:
Publishes high-quality, peer-reviewed research
Covers all aspects of research and treatment of leukemia and allied diseases
Includes studies of normal hemopoiesis due to comparative relevance
Topics of Interest:
Oncogenes
Growth factors
Stem cells
Leukemia genomics
Cell cycle
Signal transduction
Molecular targets for therapy
And more
Content Types:
Original research articles
Reviews
Letters
Correspondence
Comments elaborating on significant advances and covering topical issues