Bridging the Gap: Cost-Effective Strategies for Detecting Ph-Like B-Lineage ALL in Resource-Limited Settings.

Abstract

Acute lymphoblastic leukemia (ALL) is a complex hematologic disorder primarily affecting children, characterized by genetic mutations that disrupt normal lymphoid cell differentiation and promote abnormal proliferation. A particularly high-risk subtype, Philadelphia chromosome-like ALL (Ph-like ALL), mirrors the genetic profile of Philadelphia chromosome-positive (Ph-positive) ALL but lacks the BCR::ABL1 fusion gene. While Ph-like ALL has been extensively studied in high-income countries (HICs), it remains under-researched in low- and middle-income countries (LMICs), where resource limitations hinder accurate diagnosis and targeted therapy. This review addresses this gap by providing a comprehensive overview of the incidence, genetic landscape, and detection strategies for Ph-like ALL, with a special focus on LMICs. It underscores the prevalence of Ph-like ALL and its association with poor clinical outcomes, emphasizing the critical need for cost-effective diagnostic methodologies tailored to resource-constrained settings. Despite advancements in diagnostic technologies, such as whole gene expression profiling and next-generation sequencing, their high cost and extended turnaround times limit their feasibility in LMICs. Innovative methods, such as the PGIMER In-House Rapid and Cost-Effective (PHi-RACE) classifier, which employs real-time quantitative polymerase chain reaction (PCR), offer promising solutions by delivering high sensitivity and specificity at a significantly reduced cost. This approach is further complemented using fluorescence in situ hybridization (FISH) to characterize kinase alterations, enabling the identification of targeted therapies. This method addresses the urgent need for accessible diagnostic tools in LMICs, enabling early detection and personalized treatment planning. As the landscape of Ph-like ALL detection evolves, integrating low-cost, rapid-turnaround approaches holds significant promise for improving patient outcomes globally. This review aims to highlight the challenges and opportunities in diagnosing and treating Ph-like ALL in LMICs, fostering efforts towards more accessible and effective diagnostic strategies to enhance patient care and prognosis.