Integration of Next-Generation Sequencing in Diagnosing and Minimal Residual Disease Detection in Patients With Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia.

Abstract

Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B cell ALL. It accounts for 20% of all B cell ALL cases and is similar to BCR-ABL1 in gene expression profile but lacks BCR-ABL fusion. It is highly heterogeneous and is characterized by genetic alterations that activate kinase and cytokine receptor signaling. Most of these alterations are amenable to tyrosine kinase inhibitors. Ph-like ALL is prevalent in pediatric and young adults, more common in males, and frequently seen in patients with Hispanic ancestry. It is associated with inadequate response to induction therapy, high minimal residual disease (MRD) levels, and increased risk of relapse. Overall survival and event-free survival are also inferior in these patients as compared to non-Ph-like ALL. In the clinical practice, low-density array, real-time quantitative polymerase chain reaction (RQ-PCR), flow cytometry, fluorescence in situ hybridization are used to identify genetic alteration in these patients. With the advent of next-generation sequencing (NGS), our understanding of disease pathogenesis and precision medicine has been improved. In this review, we analyzed data from several studies that used NGS as one of the diagnostic methods to identify genomic lesions in this high-risk subtype of B cell ALL. Studies have shown that NGS is a vital technique to identify various genomic lesions at diagnosis and throughout the treatment that can be missed by the widely used current methods. NGS has improved our understanding of various genomic lesions associated with Ph-like ALL and has helped define disease pathogenesis, MRD evaluation, and stratify therapy to prevent over or under treatment. We are in the era of precision medicine. Therefore unbiased, comprehensive genomic characterization of Ph-like ALL is important to implicate treatment directed against these genomic lesions and improve outcomes in these patients. We also analyzed data from studies that compared NGS with multi-flow cytometry and RQ-PCR for the evaluation of MRD. In the future, more extensive prospective studies are required to confirm the prognostic usefulness of NGS.