Abstract

Background: T-lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with a less favorable prognosis. The genetic background of T-ALL is widely heterogeneous, with the co-occurrence of multiple genetic abnormalities. The STIL-TAL1 rearrangement results from a submicroscopic deletion on chromosome 1p33 and is present in 15 - 25% of T-ALL cases. Submicroscopic deletions are not detected by conventional cytogenetic ana-lyses but can be identified through array comparative genomic hybridization and/or high-throughput RNA sequencing. Patients with the STIL-TAL1 fusion exhibit distinct characteristics, such as a young age, high white blood cell count, typical immunophenotype, and specific genetic abnormalities. However, the clinical, laboratory, and prognostic significance of this rearrangement remains unclear. This study was performed to identify STIL-TAL1 rearrangement resulting from submicroscopic 1p33 deletion in T-ALL and to investigate the clinical, immunologic, and genetic characteristics of T-ALL patients with STIL-TAL1 fusion.
Methods: A total of 15 T-ALL patients were enrolled over a 6-year period (2018 - 2023). We evaluated clinical features and laboratory findings, including immunophenotyping, multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), karyotype analysis, next-generation sequencing (NGS), and chromosomal microarray analysis (CMA), on bone marrow or peripheral blood specimens at the diagnostic stage.
Results: Multiplex RT-PCR was performed on 15 cases of T-ALL, and STIL-TAL1 fusion was detected in 3 cases (20.0%, 3/15). STIL-TAL1-positive patients were all male, under 40 years of age, and presented with lymph node enlargement, hepatosplenomegaly, and mediastinal mass. They showed relatively higher leukocyte counts and hemoglobin levels, but lower platelet counts compared to STIL-TAL1 negative cases. Immunophenotyping analysis revealed higher sCD3 and lower CD34 expression with no aberrant myeloid lineage expression. CMA demonstrated a 63-kb heterozygous deletion at 1p33, along with additional copy number abnormalities such as TCR rearrangements and a biallelic CDKN2A deletion.
Conclusions: The T-ALL with STIL-TAL1 fusion exhibits unique clinical, immunologic, and genetic characteristics. Further multi-center studies, incorporating cytogenetic and molecular analyses, are needed to elucidate the detailed pathophysiology, characteristics, and clinical significance of this gene rearrangement.

DOI: 10.7754/Clin.Lab.2024.241025