Krstevska Bozhinovikj E, Matevska-Geshkovska N, Staninova Stojovska M, Gjorgievska E, Jovanovska A, Kocheva S, Dimovski A
Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, University Ss. Cyril and Methodius in Skopje, Mother Theresa 47, 1000 Skopje, N. Macedonia.
University Clinic for Pediatric diseases, Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, Mother Theresa 17, 1000, Skopje, N. Macedonia.
Balkan J Med Genet. 2025 Mar 6;27(2):5-12. doi: 10.2478/bjmg-2024-0020. eCollection 2024 Dec.
Although the identification of disease subtypes conveying prognostic significance along with minimal residual disease (MRD) assessment represent cornerstones for stratification in childhood acute lymphoblastic leukemia (ALL), approximately half of the relapses occur in patients from standard-risk groups. Identification of the drivers of treatment failure is crucial for detection of high-risk clones at diagnosis. We evaluated clinical variables and the most common genetic alterations in an unselected cohort of 55 patients with B-ALL treated according to the ALL-IC-BFM 2002 protocol, with a median follow-up of 46 months. Matched diagnosis-relapse samples underwent screening for additional alterations using whole-exome sequencing. Mutations in the gene were found in 80% (4/5) of the patients with relapse, either present from the disease onset or acquired at relapse, while none of the examined patients in remission presented alterations in this gene. Deletions in and (present in 2/5 and 1/5 of the patients with relapse, respectively) were infrequent or absent in the patients in remission, respectively. Screening for alterations in the gene at diagnosis and/or at multiple time-points during chemotherapy could be incorporated into treatment protocols, as it may contribute to the identification of significant number of patients with predefined or acquired chemoresistant clones.
尽管识别具有预后意义的疾病亚型以及微小残留病（MRD）评估是儿童急性淋巴细胞白血病（ALL）分层的基石，但约一半的复发发生在标准风险组的患者中。识别治疗失败的驱动因素对于在诊断时检测高危克隆至关重要。我们评估了按照ALL-IC-BFM 2002方案治疗的55例B-ALL患者的未选择队列中的临床变量和最常见的基因改变，中位随访时间为46个月。配对的诊断-复发样本使用全外显子测序进行额外改变的筛查。在80%（4/5）的复发患者中发现了该基因的突变，这些突变要么在疾病发作时就存在，要么在复发时获得，而在缓解期的所有检查患者中该基因均未出现改变。该基因的缺失（分别在2/5和1/5的复发患者中出现）在缓解期患者中分别很少见或不存在。在诊断时和/或化疗期间的多个时间点筛查该基因的改变可纳入治疗方案，因为这可能有助于识别大量具有预定义或获得性化疗耐药克隆的患者。
