Conference Abstracts - 5th Binaytara Precision Oncology Summit: Redefining Cancer Treatment with Molecular Targeted Strategies
Vol. 5, Issue Supplement 1, 2025 · S1-2
Ph-like ALL Exhibits Unique Hematological Features with CD36 Overexpression: A Diagnostic and Prognostic Analysis of 1,021 Indian Patients.
Dikshat Gopal Gupta, PhD,Monika Fnu, BHMS, MBA,Aarohan Puri, PreMed,Praveen Sharma, MD, DM,Man Updesh Singh Sachdeva, MD,Shano Naseem, MD,Parveen Bose, MSc,Jogeshwar Binota, MSc,Pankaj Malhotra, MD,Alka Khadwal, MD,Subhash Varma, MD
Submission received: 2025-07-27 / Accepted: 2025-08-27 / Published: 2025-09-26
Abstract
Background
Acute lymphoblastic leukemia (ALL) exhibits significant genetic heterogeneity, with prognostically distinct subtypes requiring precise characterization for optimal treatment. Ph-like ALL, a high-risk genetic subtype driven by kinase signaling dysregulation, poses diagnostic challenges in resource-limited settings due to its genetic complexity and lack of standardized assays. Data from low-and middle-income countries (LMICs) remain scarce, particularly regarding their immunophenotypic, molecular, and clinical features in diverse populations.
Materials & Methods
In this first comprehensive LMIC study (2017–2023), we analyzed 1,021 Indian B-ALL patients: 1) recurrent fusion screening (RT-PCR/FISH), 2) droplet digital PCR for mutation detection, 3) flow cytometry (CD36, CD13/CD33), and 4) minimal residual disease monitoring. To address diagnostic barriers, we developed the PGIMER in-house rapid and cost-effective classifier (PHi-RACE), an 8-gene expression-based tool validated against gold-standard assays.
Results
Ph-like ALL constituted 26.7% of cases, with distinct features including older age (p=0.036), male predominance (p=0.047), elevated WBC counts, and frequent CD36 expression (p<0.05). Lymphadenopathy and MRD positivity (40% vs. 19.3% in non-Ph-like) were hallmark clinical features. PHi-RACE demonstrated high accuracy (95.2% sensitivity, 83.7% specificity) and identified Ph-like ALL cases with IKZF1 deletions (18.9%), CRLF2 rearrangements (11.6%), and JAK2 mutations (e.g., R683S). Aberrant myeloid markers (CD13/CD33) were enriched in Ph-like cases (p<0.05). Regional genetic diversity was evident, with lower CRLF2 alteration rates than Western cohorts.
Discussion
Our study defines the hematological and immunophenotypic landscape of Ph-like ALL in India, highlighting CD36 as a potential diagnostic marker. PHi-RACE offers a scalable alternative to costly genomic assays, enabling rapid risk stratification in LMICs. The high MRD positivity and kinase-activating alterations underscore the need for early TKI-based interventions. Future studies incorporating PHi-RACE in multiethnic cohorts and advocating for global access to targeted therapies, addressing disparities in Ph-like ALL management.