Increased CD123 surface expression has been associated with high-risk disease characteristics in adult acute myeloid leukemia (AML), but has not been well-characterized in childhood AML. In this study, we defined CD123 expression and associated clinical characteristics in a uniformly treated cohort of pediatric patients with newly diagnosed AML enrolled on the Children's Oncology Group AAML1031 phase III trial (NCT01371981).

AML blasts within diagnostic bone marrow specimens (n = 1,040) were prospectively analyzed for CD123 protein expression by multidimensional flow cytometry immunophenotyping at a central clinical laboratory. Patients were stratified as low-risk or high-risk on the basis of (1) leukemia-associated cytogenetic and molecular alterations and (2) end-of-induction measurable residual disease levels.

The study population was divided into CD123 expression–based quartiles (n = 260 each) for analysis. Those with highest CD123 expression (quartile 4 [Q4]) had higher prevalence of high-risk KMT2A rearrangements and FLT3-ITD mutations (P < .001 for both) and lower prevalence of low-risk t(8;21), inv(16), and CEBPA mutations (P < .001 for all). Patients in lower CD123 expression quartiles (Q1-3) had similar relapse risk, event-free survival, and overall survival. Conversely, Q4 patients had a significantly higher relapse risk (53% v 39%, P < .001), lower event-free survival (49% v 69%, P < .001), and lower overall survival (32% v 50%, P < .001) in comparison with Q1-3 patients. CD123 maintained independent significance for outcomes when all known contemporary high-risk cytogenetic and molecular markers were incorporated into multivariable Cox regression analysis.

CD123 is strongly associated with disease-relevant cytogenetic and molecular alterations in childhood AML. CD123 is a critical biomarker and promising immunotherapeutic target for children with relapsed or refractory AML, given its prevalent expression and enrichment in patients with high-risk genetic alterations and inferior clinical outcomes with conventional therapy.

CD123 表面表达增加与成人急性髓性白血病 (AML) 的高危疾病特征相关，但在儿童 AML 中尚未得到充分表征。在这项研究中，我们在参加儿童肿瘤组 AAML1031 III 期试验 (NCT01371981) 的新诊断 AML 儿科患者的统一治疗队列中定义了 CD123 表达和相关临床特征。

在中央临床实验室通过多维流式细胞术免疫分型对诊断性骨髓标本 (n = 1,040) 中的 AML 母细胞进行前瞻性分析 CD123 蛋白表达。根据 (1) 白血病相关的细胞遗传学和分子改变和 (2) 诱导结束时可测量的残留疾病水平，将患者分为低风险或高风险。

研究人群被分为基于 CD123 表达的四分位数（每个 n = 260）进行分析。CD123 表达最高的那些人（四分位数 4 [Q4]）具有较高的高风险KMT2A重排和FLT3 -ITD 突变患病率（两者P < .001）和低风险 t(8;21)、inv( 16) 和CEBPA突变（所有P < .001）。处于较低 CD123 表达四分位数 (Q1-3) 的患者具有相似的复发风险、无事件生存期和总生存期。相反，Q4 患者的复发风险显着更高（53%对39%，P < .001），无事件生存率较低（49%对69%，P< .001)，与 Q1-3 患者相比，总生存率较低 (32%对50%，P < .001)。当所有已知的当代高风险细胞遗传学和分子标记被纳入多变量 Cox 回归分析时，CD123 对结果保持独立意义。

CD123 与儿童 AML 中疾病相关的细胞遗传学和分子改变密切相关。CD123 是复发或难治性 AML 儿童的关键生物标志物和有前途的免疫治疗靶点，因为它在具有高风险基因改变和常规治疗临床结果较差的患者中普遍表达和富集。