ROZŠÍŘENÁ MOLEKULÁRNÍ DIAGNOSTIKA DOSPĚLÝCH PACIENTŮ S ALL V ČR
| Title in English | Molecular Diagnostics of Adult ALL Patients in the Czech Republic |
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| Authors | |
| Year of publication | 2024 |
| Type | Conference abstract |
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| Description | Acute lymphoblastic leukemia (ALL) accounts for 20% of acute leukemias in adults. With increasing age, the proportion of prognostically unfavorable subtypes, such as BCR::ABL1-positive and BCR::ABL1-like ALL, rises. The 5-year overall survival rate is significantly lower in adult ALL patients (50%) compared to pediatric patients (90%). In 2023, within the Czech Leukemia Group for Life, we launched a multicenter initiative focusing on expanded molecular diagnostics of ALL. Modern genomic methods based on massively parallel sequencing enable reliable classification of B- or T-ALL subtypes. Transcriptome sequencing provides data on gene expression profiles, gene fusions, and somatic variants. Panel sequencing, along with whole-exome sequencing, supplements information on the occurrence of somatic variants associated with specific ALL subtypes. Another method used is MLPA/digital MLPA, which detects copy number variations (CNVs), including gene deletions and amplifications, with the ability to determine the presence of the IKZF1plus profile. As part of the expanded diagnostics, ex vivo testing of primary T-ALL patient cells for sensitivity to venetoclax and dasatinib is also conducted. The integration of these methods with standard laboratory diagnostics (cytogenetic analyses, flow cytometry, and myelogram) improves the accuracy of ALL subtype classification and risk stratification. To date, 26 patients have been examined at diagnosis (16 B-ALL, 4 MPAL, 6 T-ALL), with molecular subtypes successfully identified in all B-ALL cases (including 3× ZNF384r, 3× KMT2Ar, 2× BCR::ABL1-like, and others). Pathogenic somatic mutations were detected in all T-ALL cases and 3 out of 4 MPAL patients. The ability to classify patients according to the latest WHO 2022 and ICC 2022 classifications allows for treatment intensification in high-risk patients, thereby improving treatment success rates. |
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