Comprehensive Analysis of High-Sensitive Flow Cytometry and Molecular Mensurable Residual Disease in Philadelphia Chromosome-Positive Acute Leukemia.
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Monitoring measurable residual disease (MRD) is critical for the management of B-cell acute lymphoblastic leukemia (B-ALL). While a quantitative assessment of BCR::ABL1 transcripts is standard for Philadelphia chromosome-positive cases (Ph+ ALL), a multiparameter flow cytometry (FCM) is commonly used for MRD detection in other genetic subtypes. A total of 106 B-ALL patients underwent genetic and phenotypic analyses. Among them, 27 patients (20 adults and 7 children) harbored the t(9;22)(q34.1;q11.2) translocation and/or the BCR::ABL1 rearrangement. A high correlation between the BCR::ABL1 transcript levels (PCR-MRD) and a standardized FCM-based method for MRD detection (FCM-MRD) was observed (r = 0.7801, p < 0.001), with a concordance rate of 88% (κ = 0.761). The FCM detected MRD in 82.9% of the samples with transcript levels of > 0.01%. The CD34+CD38-/dim blast pattern was significantly more frequent in Ph+ ALL (77.7%), compared to other B-ALL cases (20.2%, p < 0.0001). Additionally, Ph+ ALL exhibited a higher expression of CD66c+/CD73+ (94.0% vs. 56.9%), CD66c+/CD304+ (58.8% vs. 6.9%), and CD73+/CD304+ (75.5% vs. 15.5%) than the other B-ALL subtypes (p < 0.001). In conclusion, this high-sensitivity FCM-MRD demonstrated comparable performance to the PCR-MRD, serving as a complementary tool for MRD assessment in Ph+ ALL. Moreover, a distinct leukemia-associated immunophenotype was identified, highlighting potential biomarkers for MRD monitoring.