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<p>Measurable residual disease (MRD) detection in T-cell acute lymphoblastic leukemia (T-ALL) remains challenging due to immunophenotypic shifts during therapy and the lack of stable, lineage-specific markers. CD48, a glycosylphosphatidylinositol-anchored protein, has emerged as a promising candidate for MRD assessment owing to its differential expression between leukemic blasts and normal lymphoid cells. This study aimed to validate the diagnostic utility of CD48 in MRD detection in T-ALL, including early T-cell precursor (ETP-ALL) and near-ETP-ALL subtypes. In this prospective cohort study, 30 bone marrow samples from patients with T-ALL, ETP-ALL, and near-ETP-ALL were analyzed, including 10 diagnostic and 20 MRD samples (post-induction and post-consolidation). Ten non-leukemic marrow samples served as controls. Multiparameter flow cytometry was performed using a standardized 12-color panel. CD48 expression was quantified as mean fluorescence intensity (MFI) and compared across leukemic blasts, mature T cells, and natural killer (NK) cells. Statistical analyses included ANOVA, t-tests and Youden’s index. CD48 expression was significantly lower in leukemic blasts (mean MFI: 1140.03; range: 115-5291) compared to mature T cells (9535.3; 697-22455) and NK cells (7953.7; 213-15119) (p &lt; 0.001). In contrast, CD2, CD5, and CD7 showed overlapping expression between leukemic and normal populations. CD48 demonstrated dim/negative expression in 86.6% of leukemic cases, with stable expression across diagnostic and MRD timepoints indicating that CD48 provided potentially useful discriminatory information that helped resolve ambiguity between leukemic blasts and immature NK cells or regenerating T-cells. No significant difference in CD48 expression was observed between T-ALL and ETP-ALL subtypes. CD48 is a robust and stable immunophenotypic marker for MRD detection in T-ALL, providing superior discrimination between leukemic blasts and normal lymphoid cells compared to conventional T-cell antigens. Incorporating CD48 into MRD panels may enhance sensitivity and specificity, particularly in cases with phenotypic evolution posttherapy. Further validation in larger, multicentre cohorts is warranted to confirm its clinical utility and prognostic relevance.</p>

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CD48 as an Adjunctive Marker for Measurable Residual Disease Detection in T-Cell Acute Lymphoblastic Leukemia

  • 期刊论文

  • 发表日期：

    2026年7月24日

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  • Sabina Langer Kumar,
  • Surbhi Dahiya,
  • Jyoti Kotwal,
  • Pallavi Prakhar,
  • Manas Kalra,
  • Nitin Gupta

摘要

Measurable residual disease (MRD) detection in T-cell acute lymphoblastic leukemia (T-ALL) remains challenging due to immunophenotypic shifts during therapy and the lack of stable, lineage-specific markers. CD48, a glycosylphosphatidylinositol-anchored protein, has emerged as a promising candidate for MRD assessment owing to its differential expression between leukemic blasts and normal lymphoid cells. This study aimed to validate the diagnostic utility of CD48 in MRD detection in T-ALL, including early T-cell precursor (ETP-ALL) and near-ETP-ALL subtypes. In this prospective cohort study, 30 bone marrow samples from patients with T-ALL, ETP-ALL, and near-ETP-ALL were analyzed, including 10 diagnostic and 20 MRD samples (post-induction and post-consolidation). Ten non-leukemic marrow samples served as controls. Multiparameter flow cytometry was performed using a standardized 12-color panel. CD48 expression was quantified as mean fluorescence intensity (MFI) and compared across leukemic blasts, mature T cells, and natural killer (NK) cells. Statistical analyses included ANOVA, t-tests and Youden’s index. CD48 expression was significantly lower in leukemic blasts (mean MFI: 1140.03; range: 115-5291) compared to mature T cells (9535.3; 697-22455) and NK cells (7953.7; 213-15119) (p < 0.001). In contrast, CD2, CD5, and CD7 showed overlapping expression between leukemic and normal populations. CD48 demonstrated dim/negative expression in 86.6% of leukemic cases, with stable expression across diagnostic and MRD timepoints indicating that CD48 provided potentially useful discriminatory information that helped resolve ambiguity between leukemic blasts and immature NK cells or regenerating T-cells. No significant difference in CD48 expression was observed between T-ALL and ETP-ALL subtypes. CD48 is a robust and stable immunophenotypic marker for MRD detection in T-ALL, providing superior discrimination between leukemic blasts and normal lymphoid cells compared to conventional T-cell antigens. Incorporating CD48 into MRD panels may enhance sensitivity and specificity, particularly in cases with phenotypic evolution posttherapy. Further validation in larger, multicentre cohorts is warranted to confirm its clinical utility and prognostic relevance.