Background
Early identification of Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is crucial for enhancing treatment outcomes and survival rates. This high-risk subtype, characterized by genetic alterations activating cytokine receptor and kinase signaling pathways, is difficult to detect in developing countries due to limited availability of specialized assays.
Objective & Methods
This study aims to identify Ph-like ALL cases using an in-house developed PHi-RACE Classifier for the first time in developing nations and to characterize the genomic alterations associated with recurrent gene abnormalities negative 108 (RGAneg) B-ALL samples. Genetic alterations were analyzed with a focus on TSLPR/CRLF2 expression, IKZF1 deletion, chimeric gene fusions, and abnormal myeloid marker expression. Minimal residual disease (MRD) positivity was compared between Ph-like and non-Ph-like ALL cases.
Results
The PHi-RACE classifier identified 34.25% (37/108) of cases as Ph-like ALL. These cases were characterized by TSLPR/CRLF2 expression (11.58%), IKZF1 deletion (18.9%), and the presence of chimeric gene fusions (34.61%). Among Ph-like ALL cases with TSLPR/CRLF2 overexpression, 33.33% exhibited CRLF2::IGH rearrangements, another 33.33% showed EPOR::IGH rearrangements, and 50% had the JAK2 mutation R683S. Aberrant expression of myeloid markers CD13 (18.91%, p=0.02) and CD33 (27.02%, p=0.05) was more prevalent in Ph-like ALL. Additionally, MRD positivity was higher in Ph-like cases (40%) compared to non-Ph-like cases (19.29%).
Conclusions
The PHi-RACE classifier demonstrated a significant incidence of Ph-like ALL and a relatively lower frequency of CRLF2 alterations and related chimeric gene fusions. Early identification at diagnosis emerges as pivotal for tailoring personalized treatment approaches, especially in resource-constrained settings with limited access to advanced diagnostic tools. Furthermore, the exceptional sensitivity (95.2%) and specificity (83.7%) of PHi-RACE, coupled with its cost-effectiveness (~USD 42/sample) and rapid turnaround time of ~4 hours, position it as a promising solution for efficient and accurate detection of Ph-like ALL cases.