Baldzhieva Alexandra, Burnusuzov Hasan, Andreeva Hristina, Kalfova Teodora, Petrov Steliyan, Dudova Dobrina, Vaseva Katya, Murdjeva Marianna, Taskov Hristo
Department of Medical Microbiology and Immunology "Prof. Dr. Elissay Yanev", Faculty of Medicine, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria.
Research Institute at Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria.
Int J Mol Sci. 2025 Apr 30;26(9):4282. doi: 10.3390/ijms26094282.
Measurable Residual Disease (MRD) assessment in pediatric acute lymphoblastic leukemia (ALL) is crucial for relapse prediction and treatment guidance. Multiparameter flow cytometry (MFC) enhances detection but faces limitations due to insufficient leukemia-associated immunophenotypes (LAIPs) and antigen modulation. This study explores new markers to improve MFC-based MRD detection in B-cell precursor ALL (BCP-ALL). Expression-patterns of seven aberrancy markers, i.e., CD44, CD304, CD73, CD86, CD123, CD99, CD58, and one B-cell maturation marker, CD22, were studied in 143 samples with leukemic-blasts from sixty-one childhood BCP-ALL patients and in hematogones of 20 non-leukemic bone marrow (BM) samples using fourteen-color MFC. The highest relative frequences of LAIPs amounted to 82.50%, reported for CD99 and CD58, followed by CD44 (81.10%), CD73 (76.20%), CD22 (73.40%), CD304 and CD86 (68.50%), while the lowest relative frequence was CD123 (44.40%). Differential expression of CD58, CD304, and CD73 in diagnostic samples was highly significant ( < 0.01) between pre-B-I, pre-B-II, immature B cells, and BCP-ALL blasts. In MRD-positive samples CD73 showed significantly high ( < 0.01) differential expression between all stages of hematogones and residual blasts, followed by CD304, CD58, and CD22. CD73 and CD304 were identified as the most reliable among the tested markers for distinguishing both diagnostic and MRD blasts from normal B cell precursors.
小儿急性淋巴细胞白血病(ALL)中的可测量残留病(MRD)评估对于复发预测和治疗指导至关重要。多参数流式细胞术(MFC)增强了检测能力,但由于白血病相关免疫表型(LAIPs)不足和抗原调节而面临局限性。本研究探索新的标志物以改善基于MFC的B细胞前体ALL(BCP-ALL)中MRD的检测。使用十四色MFC研究了61例儿童BCP-ALL患者的143份白血病母细胞样本及20份非白血病骨髓(BM)样本的造血细胞中7种异常标志物(即CD44、CD304、CD73、CD86、CD123、CD99、CD58)和1种B细胞成熟标志物CD22的表达模式。LAIPs的最高相对频率为82.50%(CD99和CD58),其次是CD44(81.10%)、CD73(76.20%)、CD22(73.40%)、CD304和CD86(68.50%),而最低相对频率是CD123(44.40%)。CD58、CD304和CD73在诊断样本中的差异表达在pre-B-I、pre-B-II、未成熟B细胞和BCP-ALL母细胞之间具有高度显著性(<0.01)。在MRD阳性样本中,CD73在造血细胞各阶段与残留母细胞之间显示出显著高的差异表达(<0.01),其次是CD304、CD58和CD22。在测试的标志物中,CD73和CD304被确定为区分诊断性和MRD母细胞与正常B细胞前体最可靠的标志物。