Comprehensive Analysis of High-Sensitive Flow Cytometry and Molecular Mensurable Residual Disease in Philadelphia Chromosome-Positive Acute Leukemia.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Neoplasm, Residual*/genetics ; Neoplasm, Residual*/diagnosis ; Flow Cytometry*/methods ; Philadelphia Chromosome*; Humans ; Male ; Female ; Adult ; Child ; Middle Aged ; Adolescent ; Aged ; Young Adult ; Child, Preschool ; Fusion Proteins, bcr-abl/genetics ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology

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.

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25000.055356/2015-04 PROGRAMA NACIONAL DE APOIO À ATENÇÃO ONCOLÓGICA (PRONON)

Keywords: Philadelphia chromosome-positive acute leukemia; acute lymphoblastic leukemia; chronic myeloid leukemia blast phase; flow cytometry; leukemia associated-immunophenotype; measurable residual disease

EC 2.7.10.2 (Fusion Proteins, bcr-abl)

Date Created: 20250313 Date Completed: 20250313 Latest Revision: 20250315

20250315

PMC11900146

10.3390/ijms26052116

40076750