Pediatric Hematology/Oncology Unit, HOMI Fundación Hospital Pediátrico la Misericordia, Bogotá, Colombia.
Grupo Oncohematología Pediátrica, Universidad Nacional de Colombia, Bogotá, Colombia.
Cancer Rep (Hoboken). 2022 May;5(5):e1587. doi: 10.1002/cnr2.1587. Epub 2021 Nov 17.
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subtype of pediatric leukemia with high risk factors and poor outcome. There are few reports of its prevalence in Latin America.
This study evaluated the frequency and clinical and biological characteristics of Ph-like ALL in a pediatric cancer center in Colombia.
The Ph-like genetic profile was analyzed by a low-density array (LDA). Samples from patients with Ph-like ALL were analyzed by fluorescent in situ hybridization for cytokine receptor like factor 2 (CRLF2) and ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) rearrangements. Copy number variations were assessed by multiplex ligation probe amplification.
Data from 121 patients were analyzed. Fifteen patients (12.4%) had Ph-like ALL, and these patients had significantly higher leukocyte counts at diagnosis and higher levels of minimal residual disease on days 15 and 33 of induction than patients without the Ph-like subtype. There were no significant differences in sex, age, or response to prednisone at day 8 between the two groups. CRLF2 rearrangements were identified in eight patients, and ABL1 rearrangements were identified in two patients. Other genetic alterations alone or in combination were identified in 77% of patients, including deletions in cyclin dependent kinase inhibitor 2 A/B (46.2%), IKAROS family zinc finger 1 (38.3%), and paired box 5 (30.8%).
Ph-like ALL had a 12.4% prevalence in our cohort of patients with pediatric ALL. The identification of this group of patients has importance for risk stratification and future targeted therapy.
费城样(Ph-like)急性淋巴细胞白血病(ALL)是一种具有高风险因素和不良预后的儿科白血病亚型。在拉丁美洲,关于其流行率的报道很少。
本研究评估了哥伦比亚一家儿科癌症中心 Ph-like ALL 的频率以及临床和生物学特征。
通过低密度阵列(LDA)分析 Ph-like 遗传谱。通过荧光原位杂交分析 Ph-like ALL 患者的细胞因子受体样因子 2(CRLF2)和 ABL 原癌基因 1,非受体酪氨酸激酶(ABL1)重排。通过多重连接探针扩增评估拷贝数变异。
分析了 121 名患者的数据。15 名患者(12.4%)患有 Ph-like ALL,这些患者在诊断时的白细胞计数明显更高,在诱导的第 15 天和第 33 天的微小残留疾病水平也更高。两组患者在性别、年龄或第 8 天泼尼松反应方面无显著差异。8 名患者存在 CRLF2 重排,2 名患者存在 ABL1 重排。77%的患者存在其他遗传改变,包括单独或联合的周期蛋白依赖性激酶抑制剂 2A/B 缺失(46.2%)、IKAROS 家族锌指蛋白 1(38.3%)和配对盒 5(30.8%)。
在我们儿科 ALL 患者队列中,Ph-like ALL 的患病率为 12.4%。鉴定出这组患者对于风险分层和未来的靶向治疗具有重要意义。