Pb1723: clinical and genetic characteristics of t-cell acute lymphoblastic leukemia with stil-tal1 fusion

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy and is associated with a less favorable outcome. The genetic background of T-ALL is widely heterogeneous and TAL1 gene is overexpressed in approximately half of the cases. A submicroscopic interstitial deletion on chromosome 1p33 results in STIL-TAL1 fusion, causing inappropriate overexpression of TAL1, which promotes T cell leukemogenesis. Submicroscopic deletions are not detected by conventional cytogenetic analyses, but by array comparative genomic hybridization and/or high-throughput sequencing. T-ALL with STIL-TAL1 fusion exhibits distinct characteristics, such as tyipical immunophenotype, karyotype, and poor treatment response. However, the clinical relevance and prognostic value of this rearrangement remain unclear. Aims: This study was performed to identify a submicroscopic deletion of 1p33 in a case of T-ALL with STIL-TAL1 fusion and investigate its pathophysiology and clinical significance based on clinical, laboratory and genetic findings. Methods: A total of 14 T-ALL patients was 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, next-generation sequencing (NGS), and chromosomal microarray analysis (CMA) on the bone marrow or peripheral blood specimen at the diagnostic stage. Results: Mutliplex RT-PCR with HemaVision (DNA Diagnostic A/S, Risskov, Denmark) was performed on 14 cases with T-ALL, and STIL-TAL1 fusion transcript was detected in 3 cases (21.4%, 3/14). STIL-TAL1 positive cases were all male children or young adult with lymph node enlargement, hepatosplenomegaly and mdiastinal mass. They showed relatively higher leukocyte counts and hemoglobin, but lower PLT results compared to STIL-TAL1 negative cases. Immunophenotyping analysis revealed more sCD3 and lesser CD34 expression with no aberrant myeloid lineage expression. CMA using CytoScan DX Assay (Thermo Fisher Scientific Inc, Frederick, USA) based on GRCh37/hg19 assembly, demonstrated a 63-kb heterozygous deletion at 1p33 with additional copy number abnormalities. Summary/Conclusion: The T-ALL with STIL-TAL1 fusion has unique clinical, laboratory and genetic characteristics. However, further muti-center studies, including cytogenetic and molecular analyses, are needed to determine more detailed pathophysiology and clinical significance for this rare gene rearrangement. Table 1. Laboratory findings in STIL-TAL1 positive and negative T-cell acute lymphoblastic leukemia - Total(n = 14) STIL-TAL1 positive(n = 3) STIL-TAL1 negative(n = 11) WBC count, ×109/L Median value (range) 84.5 (2.8–388.9) 205.6 (197.6–208.8) 47.7 (2.8–388.9) <20 2 0 (0) 2 (18.2) 20–49 4 0 (0) 4 (36.4) 50–99 2 0 (0) 2 (18.2) ≥100 6 3 (100) 3 (27.3) Hb, g/dL Median value (range) 10.8 (8.4–14) 11.6 (11.1–12.7) 9.9 (8.4–14.0) <10 6 0 (0) 6 (54.5) ≥10 8 3 (100) 5 (45.5) Platelet count, ×109/L Median value (range) 99.5 (16–212) 72 (16–77) 111 (31–212) <100 7 3 (100) 4 (36.4) ≥100 7 0 (0) 7 (63.6) Immunopheotype cCD3 12 3 (100) 9 (81.8) CD3 4 2 (66.6) 2 (18.2) CD5 13 3 (100) 10 (90.9) CD7 14 3 (100) 11 (100) CD34 8 1 (33.3) 7 (63.6) TdT 5 1 (33.3) 4 (36.4) Myeloid (CD13,33,117) 6 0 (0) 6 (54.5) Multiplex RT-PCR Detected 4 3 (100)- STIL/TAL1 1 (9.1)- KMT2A/ELL Not detected 10 0 (0) 10 (90.9) Karyotype Normal 4 0 (0) 4 (36.4) Abnormal 10 3 (100) 7 (63.6) Data are presented as medians (ranges) or numbers (percentages). Abbreviations: WBC, white blood cell; Hb, hemoglobin; RT-PCR, reverse transcriptase-polymerase chain reaction Keywords: T cell acute lymphoblastic leukemia, RT-PCR, TAL1, Microarray analysis