Optical Genome Mapping of BCL11B::TLX3-Rearranged Pediatric T-ALL: A Recurrent Structural Subgroup and Its Co-Occurring Genomic Alterations

@article{ozygala2026optical,
  title = {{Optical Genome Mapping of BCL11B::TLX3-Rearranged Pediatric T-ALL: A Recurrent Structural Subgroup and Its Co-Occurring Genomic Alterations}},
  author = {Ozygała A and Szpala J and Malm M and Stelmach M and Latoch E and Lejman M},
  journal = {The Application of Clinical Genetics},
  year = {2026},
  month = nov,
  url = {https://www.dovepress.com/optical-genome-mapping-of-bcl11btlx3-rearranged-pediatric-t-all-a-recu-peer-reviewed-fulltext-article-TACG},
  note = {CC BY},
}

TY  - JOUR
TI  - Optical Genome Mapping of BCL11B::TLX3-Rearranged Pediatric T-ALL: A Recurrent Structural Subgroup and Its Co-Occurring Genomic Alterations
AU  - Ozygała A
AU  - Szpala J
AU  - Malm M
AU  - Stelmach M
AU  - Latoch E
AU  - Lejman M
PY  - 2026
DA  - 2026/11/08
JO  - The Application of Clinical Genetics
UR  - https://www.dovepress.com/optical-genome-mapping-of-bcl11btlx3-rearranged-pediatric-t-all-a-recu-peer-reviewed-fulltext-article-TACG
AB  - Aleksandra Ozygała,1 Joanna Szpala,2 Maria Malm,3 Magdalena Stelmach,4 Eryk Latoch,5 Monika Lejman2 1Doctoral School, Medical University of Lublin, Lublin, Poland; 2Independent Genetic Diagnostics Laboratory, Department of Pediatrics, Medical University of Lublin, Lublin, Poland; 3Department of Medical Informatics and Statistics with E-learning Laboratory, Medical University of Lublin, Lublin, Poland; 4Department of Genetic Diagnostics, University Children’s Hospital of Lublin, Lublin, Poland; 5Department of Neurology and Pediatrics, Medical University of Bialystok, Białystok, PolandCorrespondence: Monika Lejman, Independent Genetic Diagnostics Laboratory, Department of Pediatrics, Medical University of Lublin, Prof. Antoni Gębala 6 Street, Lublin, 20-093, Poland, Tel +48 81 71 85 211, Email [email protected]: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy characterized by molecular abnormalities that influence clinical course and prognosis. Conventional techniques such as flow cytometry, fluorescence in situ hybridization (FISH), and karyotyping, do not enable genome-wide analysis and may miss rare aberrations, such as BCL11B::TLX3. Moreover, standard biomarkers provide insufficient prognostic information for patient stratification.Study Design: In this retrospective, single-centre study we have analysed the data of pediatric patients diagnosed with T-ALL at the Medical University of Lublin, Poland, between years 2024 and 2026, using optical genome mapping (OGM). Cases with rearrangements involving the TLX3 locus (5q35) and the BCL11B locus (14q32) were selected for detailed analysis.Results: Among 53 pediatric T-ALL patients analysed by OGM, BCL11B::TLX3 was the most frequent recurrent structural rearrangement, identified in 11 patients (20.8%). OGM detected the underlying t(5;14)(q35.1;q32.2) genome-wide and without prior targeting, including cases cryptic to conventional karyotyping, in all 11 patients, each confirmed by FISH; the translocation was balanced in 7. The rearrangement consistently co-occurred with additional lesions, most notably 9p21.3 region (MTAP/CDKN2A/CDKN2B) deletion in 9 of 11 patients, alongside MYB/AHI1 and ABL1/NUP214 duplications and further inter- and intrachromosomal rearrangements, confirming that BCL11B::TLX3 is not an isolated event. In a single assay, OGM resolved a broad spectrum of structural and copy-number alterations, with deletions most frequent; copy-number findings were concordant with chromosomal microarray analysis in 5 of 9 evaluable cases. Exploratory analyses showed no statistically significant association between the detected alterations and early treatment response (day 15 FCM-MRD, day 33 PCR-MRD).Conclusion: OGM expands genome-wide analysis in T-ALL diagnostics. As a high-resolution, unbiased technique, it detects cryptic and rare rearrangements together with their co-occurring genomic context, and represents a complementary cytogenomic tool whose clinical utility requires validation in larger, prospective cohorts.Keywords: T-cell acute lymphoblastic leukemia, BCL11B::TLX3, optical genome mapping, molecular diagnostics
SN  - 1178-704X
ER  -