Toloza María Jazmín, Lincango Marco, Camacho María Fernanda, Ledesma Martin Manuel, Enrico Alicia, Moiraghi Beatriz, Tosin Fernanda, Mariano Romina, Pérez Mariel, Aranguren Pedro Negri, Riva María Elisa, Larripa Irene B, Belli Carolina B
Laboratorio de Genética Hematológica, Instituto de Medicina Experimental, IMEX-CONICET/ Academia Nacional de Medicina, Pacheco de Melo 3081, Ciudad Autónoma de Buenos Aires, C1425AUM, Argentina.
Hospital de Alta Complejidad en Red El Cruce "Dr. Néstor C. Kirchner", Florencio Varela, Buenos Aires, Argentina.
Ann Hematol. 2024 Dec;103(12):5249-5260. doi: 10.1007/s00277-024-06074-3. Epub 2024 Nov 7.
The immune system of chronic myeloid leukemia (CML) patients is severely impaired, hampering anti-tumor responses, and maximal immune recovery occurs after achieving deep molecular responses to tyrosine kinase inhibitors. This study aimed to discern the expression patterns of NCR2, IL2, IL4, EOMES, FOXP3, GATA3, RORGT, PD1/PDL1 and TIM3/GAL9, expanding our previous dataset up to 19 key immune mediators, during the initial year on imatinib. Gene expression dynamics were evaluated in 171 peripheral blood samples from 89 CML patients, including 43 longitudinally monitored individuals, and 52 healthy donors. Univariate and unsupervised analyses confirmed diminished expression of most studied immune mediators, except for TNF, ARG1 and IL4, differentiating between baseline and 3-month samples. Most of the studied mediators normalized along treatment, with a transient increase of TNF and IL6 levels at 3-months, especially in optimal responders (BCR::ABL1 < 0.1%). Univariate and multivariate analyses showed heightened ARG1 levels and a transition from PD1/PDL1 dominance at 3 months to TIM3/GAL9 at 12 months in non-optimal responders (BCR::ABL1 ≥ 0.1%). Our longitudinal design offers a deeper exploration of immune gene expression dynamics in CML patients on imatinib, highlighting its potential implications for therapy outcomes.
慢性髓性白血病（CML）患者的免疫系统严重受损，阻碍了抗肿瘤反应，并且在对酪氨酸激酶抑制剂实现深度分子反应后会出现最大程度的免疫恢复。本研究旨在识别NCR2、IL2、IL4、EOMES、FOXP3、GATA3、RORGT、PD1/PDL1和TIM3/GAL9的表达模式，将我们之前的数据集扩展至19种关键免疫介质，这些介质是在接受伊马替尼治疗的第一年期间进行观察的。对来自89例CML患者的171份外周血样本（包括43例纵向监测的个体）以及52名健康供体的样本进行了基因表达动态评估。单变量和无监督分析证实，除TNF、ARG1和IL4外，大多数研究的免疫介质表达降低，这在基线样本和3个月时的样本之间存在差异。大多数研究的介质在治疗过程中恢复正常，TNF和IL6水平在3个月时短暂升高，尤其是在最佳反应者中（BCR::ABL1 < 0.1%）。单变量和多变量分析显示，在非最佳反应者中（BCR::ABL1 ≥ 0.1%），ARG1水平升高，且从3个月时的PD1/PDL1主导状态转变为12个月时的TIM3/GAL9主导状态。我们的纵向研究设计更深入地探索了接受伊马替尼治疗的CML患者的免疫基因表达动态，突出了其对治疗结果的潜在影响。
