Lu D L, Zhang Q M, Li L, Gu R X
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China.
Zhonghua Xue Ye Xue Za Zhi. 2025 Jul 14;46(7):668-672. doi: 10.3760/cma.j.cn121090-20250228-00099.
The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph(+) ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph(+) ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.
基于分子遗传学改变和微小残留病（MRD）监测的不断发展的分层治疗方法，为临床管理费城染色体阳性急性淋巴细胞白血病（Ph(+) ALL）奠定了坚实基础。然而，随着免疫靶向治疗的广泛应用和检测技术灵敏度的提高，一些Ph(+) ALL患者在MRD评估中出现了差异，特别是与其他方法检测到的水平相比，基于BCR::ABL1的MRD水平持续升高。研究表明，这种持续的BCR::ABL1阳性可能不仅仅反映残留的淋巴母细胞，还可能表明多谱系造血细胞的参与。这种独特的生物学特征被称为多谱系受累的Ph(+) ALL。目前，该亚型缺乏标准化的诊断标准和预后框架，给临床决策带来了重大挑战。因此，本文对其分子和病理特征、潜在的预后生物标志物、疾病演变模式及临床意义进行了全面综述，旨在为更准确的诊断和治疗策略提供依据。
