Sultan Mona, Ibrahim Maha S M, Abdur-Rahman Mariam, Dessouki Omar F A, Ebeid Emad N, Eldesouky Mohamed A
Division of Biochemistry, Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
Department of Clinical Pathology, National Cancer Institute, Cairo University, Giza, Egypt.
Egypt J Immunol. 2025 Jul;32(3):48-58. doi: 10.55133/eji.320306.
Acute myeloid leukemia (AML) is a hematological ailment characterized via specific clinical and molecular heterogeneous disorders. It is associated with poor long-term survival, even with new chemotherapy regimens. T-cell immunoglobulin and mucin domain-3 (TIM-3) is a membrane protein expressed in various kinds of immune cells. Recent studies reported that higher TIM-3 expression levels correlate with advanced tumor stages and poor prognosis in several solid tumors. This study aimed to evaluate the expression of TIM-3 as a specific marker of leukemia stem cells (LSCs) in pediatric patients with newly diagnosed AML, and its possible role as a prognostic biomarker. The expression levels of TIM-3 were assessed in the bone marrow aspirate (BMA) of 32 newly diagnosed pediatric AML cases and 10 control subjects by flow cytometry on (CD34+/CD38+) fraction, as well as on (CD34+/CD38-) fraction, at the time of diagnosis and at the end of the first cycle of chemotherapy (first induction). These expression levels in patients were then correlated with clinical outcome. TIM-3 expression levels were significantly higher in pediatric AML patients on LSCs (CD34+/CD38-) and leukemic progenitors (CD34+/CD38+) fractions compared to the control group (p-value < 0.001). TIM-3 expression levels on LSCs (CD34+/CD38-) fraction were associated with a higher mortality risk and short survival. In conclusion, T-cell immunoglobulin and mucin domain-3 (TIM-3) may serve as LSCs specific biomarker for poor prognosis in pediatric AML patients.
急性髓系白血病（AML）是一种血液疾病，其特征在于特定的临床和分子异质性疾病。即使采用新的化疗方案，它也与长期生存率低相关。T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）是一种在各种免疫细胞中表达的膜蛋白。最近的研究报道，在几种实体瘤中，较高的TIM-3表达水平与肿瘤晚期和预后不良相关。本研究旨在评估TIM-3作为新诊断的小儿AML患者白血病干细胞（LSCs）特异性标志物的表达，及其作为预后生物标志物的可能作用。通过流式细胞术对32例新诊断的小儿AML病例和10例对照受试者的骨髓抽吸物（BMA）在诊断时和化疗第一周期（首次诱导）结束时的（CD34+/CD38+）部分以及（CD34+/CD38-）部分评估TIM-3的表达水平。然后将患者的这些表达水平与临床结果相关联。与对照组相比，小儿AML患者LSCs（CD34+/CD38-）和白血病祖细胞（CD34+/CD38+）部分的TIM-3表达水平显著更高（p值<0.001）。LSCs（CD34+/CD38-）部分的TIM-3表达水平与更高的死亡风险和短生存期相关。总之，T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）可能作为小儿AML患者预后不良的LSCs特异性生物标志物。
