Abstract
Ph-like ALL, a high-risk subgroup of B-cell ALL, is associated with a poor prognosis. The genetic diversity observed across different ethnicities underscores the importance of population-specific studies to gain a deeper understanding of its genetic drivers and clinical outcomes. This study aims to characterize the Ph-like ALL group in Turkish pediatric B-ALL patients and evaluate our custom-developed gene panel for subgroup identification. To identify the Ph-like subgroup, RNA was isolated from 35 bone marrow samples, and targeted mRNA expression analysis was performed by RT-qPCR using a custom-designed panel consisting of 96 genes. Additionally, the Archer FusionPlex ALL Panel (ArcherDX, Boulder, CO) was employed for further evaluation of patients demonstrating the highest similarity rates. This study employed a gene panel designed to differentiate Turkish Ph-like ALL patients within the Ph-negative group, identifying two Ph-like cases (6%). The panel demonstrated 96.9% sensitivity and 93.9% specificity in detecting Ph-like ALL, highlighting its effectiveness in differential diagnosis. In the Ph-like cases, alterations in PAX5 (rs143723948, rs879020782) and IKZF1 (rs6975767) were observed. Both cases shared a novel EPOR variant (rs1312770718), with no known clinical impact. Additionally, a novel variantin the PTPN11 gene was interpreted as “Possibly Damaging”. This study introduces a gene profiling-based diagnostic approach for the Ph-like subgroup of pediatric B-ALL in Turkish patients. The integration of targeted tyrosine kinase inhibitors into treatment protocols, guided by the diagnostic algorithm, aims to improve prognosis and survival, advancing personalized management of Ph-like ALL.