Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany.
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
Am J Hematol. 2017 Apr;92(4):388-396. doi: 10.1002/ajh.24663. Epub 2017 Feb 21.
In acute myeloid leukemia (AML), leukemia-initiating cells exist within the CD34+/CD38- cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38- cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft-versus-leukemia effects. Percentage of bone marrow CD34+/CD38- cell burden at diagnosis was measured using flow cytometry and was highly variable (median 0.5%, range 0%-89% of all mononuclear cells). A high CD34+/CD38- cell burden at diagnosis associated with worse genetic risk and secondary AML. Patients with a high CD34+/CD38- cell burden had shorter relapse-free and overall survival which may be mediated by residual leukemia-initiating cells in the CD34+/CD38- cell population, escaping the graft-versus-leukemia effect after allogeneic transplantation. Evaluating the CD34+/CD38- cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic transplantation. Further studies to understand leukemia-initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.
在急性髓细胞白血病(AML)中,白血病起始细胞存在于 CD34+/CD38-细胞群中。它们被认为对化疗更具抵抗力,富含微小残留疾病细胞群体,并负责复发。在这里,我们评估了在 169 例接受完全缓解后异体干细胞移植的 AML 患者中,高诊断 CD34+/CD38-细胞负担的临床和生物学相关性及其预后影响。在这里,治疗方法主要基于免疫性移植物抗白血病效应。使用流式细胞术测量诊断时骨髓 CD34+/CD38-细胞负担的百分比,其变化很大(中位数为 0.5%,范围为所有单核细胞的 0%-89%)。高诊断时的 CD34+/CD38-细胞负担与更高的遗传风险和继发性 AML 相关。高 CD34+/CD38-细胞负担的患者无复发生存期和总生存期较短,这可能是由于 CD34+/CD38-细胞群中残留的白血病起始细胞逃避了异体移植后的移植物抗白血病效应。评估诊断时的 CD34+/CD38-细胞负担可能有助于识别异体移植后复发风险较高的患者。需要进一步研究以了解白血病起始细胞生物学并开发靶向治疗方法,以改善 AML 患者的预后。