Clinical pathology, National Cancer Institute, Cairo University, Egypt.
Pediatric Oncology, National Cancer Institute, Cairo University, Egypt.
Exp Mol Pathol. 2021 Feb;118:104597. doi: 10.1016/j.yexmp.2020.104597. Epub 2020 Dec 23.
Acute myeloid leukemia (AML) accounts for approximately 20% of all pediatric acute leukemias. The outcome of AML is still unsatisfactory. CD123 and CD200 were demonstrated to play important roles in hematological malignancies. The aim of this study was to investigate the impact of CD200 and CD123 overexpression and the influence of both proteins on the clinical presentation and disease outcome. Bone marrow (BM) samples from 89 pediatric AML patients were obtained at presentation and after therapy. Cells from the bulk population and from the leukemia stem cell (LSC) compartment were examined by multi parametric flow cytometry. In the bulk population, CD200 was positive in 64/89 (71.9) samples, CD123 was positive in 62/89 (69.7%) samples, and dual CD200 and CD123 positivity was observed in 54/89 (60.7%) samples. CD200/CD123 expressions were observed in LSCs in 64/60 samples respectively (71.9%/67.4%), and co-expressed in 51 samples (57.3%). CD200 was overexpressed in secondary AML (p < 0.05). A multivariate analysis revealed that minimal residual disease (MRD) and lymphadenopathy were associated with CD200 overexpression. Moreover, lymphadenopathy, low platelet count, and MRD were independently associated with CD123 expression. The co-expression of CD200 and CD123 demonstrated a statistically significant relationship with unfavorable cytogenetic karyotypes and high total leucocyte count (TLC). The expression of CD200 and CD123 alone and together had an adverse impact on complete remission (CR), MRD positivity, and overall survival (OS). Cases with MRD on day 28 after induction displayed stable expression patterns of CD200 and CD123. CD200 and CD123 both had a negative influence on clinical presentation and treatment outcome, which remarkably worsened when both were concomitantly overexpressed. CD200 and CD123 can therefore be used as markers of MRD in AML and may also serve as therapeutic targets.
急性髓系白血病（AML）约占所有儿科急性白血病的 20%。AML 的治疗效果仍不令人满意。CD123 和 CD200 已被证明在血液系统恶性肿瘤中发挥重要作用。本研究旨在探讨 CD200 和 CD123 过表达的影响，以及这两种蛋白对临床表现和疾病结局的影响。在治疗前和治疗后，从 89 例儿科 AML 患者的骨髓（BM）样本中获得了细胞。使用多参数流式细胞术检查了来自大量细胞群和白血病干细胞（LSC）区室的细胞。在大量细胞群中，64/89（71.9%）样本中 CD200 阳性，62/89（69.7%）样本中 CD123 阳性，54/89（60.7%）样本中同时存在 CD200 和 CD123 阳性。在 60 个样本中的 64 个样本（71.9%/67.4%）中观察到 CD200/CD123 表达，并在 51 个样本（57.3%）中共同表达。在继发性 AML 中 CD200 过表达（p<0.05）。多变量分析显示，微小残留病（MRD）和淋巴结病与 CD200 过表达相关。此外，淋巴结病、血小板计数低和 MRD 与 CD123 表达独立相关。CD200 和 CD123 的共表达与不良细胞遗传学核型和总白细胞计数（TLC）高呈统计学显著关系。CD200 和 CD123 的单独和共同表达对完全缓解（CR）、MRD 阳性和总生存（OS）有不良影响。诱导后第 28 天 MRD 阳性的病例显示 CD200 和 CD123 的稳定表达模式。CD200 和 CD123 对临床表现和治疗结果均有负面影响，当两者同时过表达时，情况明显恶化。因此，CD200 和 CD123 可用作 AML 中 MRD 的标志物，也可用作治疗靶点。
