Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML

IF 13.4 1区 医学 Q1 HEMATOLOGY
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
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引用次数: 0

Abstract

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.

Abstract Image

诊断时的粒细胞丰度和成熟状态预测CML的无治疗缓解
无治疗缓解(TFR)已成为慢性粒细胞白血病(CP CML)的治疗目标。然而,目前还没有标准化的生物标志物用于临床应用。在这项多中心研究中,我们探讨了骨髓(BM)细胞形态学在临床诊断中的全球可及性和不可或缺的作用。我们纳入了来自7个临床站点的113例CP CML患者的诊断性BM抽吸样本,这些患者曾尝试首次停用TKI。我们将细胞形态学幻灯片数字化成100倍放大的高分辨率图像,并使用基于深度学习的图像分析对这些图像进行分析。我们分析了CP CML患者的骨髓细胞形态学指纹图谱,并与942例对照骨髓样本进行了比较,总结了已知的粒细胞优势和淋巴细胞、单核细胞和红细胞的减少。我们发现中性粒细胞丰度和粒细胞成熟与持续的TFR有关。我们从视觉上证实了这些,并证明了它们对已知临床因素的独立影响。我们的研究强调了计算骨髓细胞形态学识别新的临床生物标志物的潜力,并表明诊断时粒细胞扩张和成熟可以反映影响TFR维持的内在疾病病理。
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
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
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