STAG2 PROTEIN EXPRESSION IN ADOLESCENT, YOUNG ADULT, AND ELDER PATIENTS WITH MYELODYSPLASTIC NEOPLASMS: ASSOCIATION WITH CYTOGENETIC ALTERATIONS AND THERAPEUTIC IMPLICATIONS

@article{silva2026stag2,
  title = {{STAG2 PROTEIN EXPRESSION IN ADOLESCENT, YOUNG ADULT, AND ELDER PATIENTS WITH MYELODYSPLASTIC NEOPLASMS: ASSOCIATION WITH CYTOGENETIC ALTERATIONS AND THERAPEUTIC IMPLICATIONS}},
  author = {Beatriz FERREIRA DA SILVA and Nina CARROSSINI BASTOS and Tatiana FONSECA ALVARENGA and Rafael MINA PIERGIORGE and Verônica GOULART MOREIRA and Ana Paula BUENO and Cristiane BEDRAN MILITO and Cíntia Barros SANTOS-REBOUÇAS and Teresa de Souza FERNANDEZ},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107969},
  url = {https://doi.org/10.1016/j.htct.2026.107969},
  note = {CC BY},
}

TY  - JOUR
TI  - STAG2 PROTEIN EXPRESSION IN ADOLESCENT, YOUNG ADULT, AND ELDER PATIENTS WITH MYELODYSPLASTIC NEOPLASMS: ASSOCIATION WITH CYTOGENETIC ALTERATIONS AND THERAPEUTIC IMPLICATIONS
AU  - Beatriz FERREIRA DA SILVA
AU  - Nina CARROSSINI BASTOS
AU  - Tatiana FONSECA ALVARENGA
AU  - Rafael MINA PIERGIORGE
AU  - Verônica GOULART MOREIRA
AU  - Ana Paula BUENO
AU  - Cristiane BEDRAN MILITO
AU  - Cíntia Barros SANTOS-REBOUÇAS
AU  - Teresa de Souza FERNANDEZ
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107969
UR  - https://doi.org/10.1016/j.htct.2026.107969
AB  - Background: Myelodysplastic neoplasms (MDS) are characterized by biological and clinical heterogeneity and an intrinsic risk of progression to acute myeloid leukemia (AML). MDS is the most frequent hematopoietic neoplasm in elders, being rare in individuals younger than 40 years of age. Cytogenetic analysis plays an important role in the diagnosis, prognosis and treatment selection of MDS. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for MDS. But, due to its associated morbidity, is generally indicated for younger and higher-risk patients, highlighting the need for biomarkers capable of improving prognostic stratification and therapeutic opportunities. The cohesin complex ensures sister chromatid cohesion, 3D chromatin architecture, and DNA damage repair, with the STAG2 subunit being the component most frequently altered in myeloid neoplasms. However, STAG2 protein expression, its association with karyotype and potential as a therapeutic target, remains underexplored in MDS. Aim: To compare STAG2 protein expression between adolescent and young adult (AYA) and elder (≥60) patients with MDS, investigate its association with cytogenetic abnormalities, and assess its potential as a biomarker. Methods: We analyzed 23 AYA and 29 elder MDS patients. Cytogenetics were performed in bone marrow (BM) cells by G-banding and FISH. STAG2 protein expression was evaluated by immunohistochemistry in BM biopsies from patients and neoplasm-free controls. Results: Cytogenetic abnormalities were found in 22/53 (39.6%) patients (50% AYA vs 31% elders). Disease progression was observed in 19/53 (36%) patients (29% AYA vs 41.4% elders). The most frequent cytogenetic alterations were -7, +8, del(17p), and complex karyotypes. All healthy controls had high STAG2 expression, whereas 33/53 (60.4%) MDS patients showed reduced expression (54.2% AYA vs 69% elders). Reduced STAG2 expression was similar among patients with normal and abnormal karyotypes in both age groups. However, regarding specific cytogenetic alterations, all patients harboring +8 and complex karyotypes showed reduced STAG2 expression in both age groups. Discussion: Complex karyotypes are recognized as poor or very poor-risk cytogenetic alteration in MDS, whereas trisomy 8 is classified as intermediate-risk. Nevertheless, previous studies have reported that +8 may show worse outcomes than other alterations in this risk group. In our cohort, both trisomy 8 and complex karyotypes were consistently associated with reduced STAG2 expression, suggesting a potential association between impaired cohesin function and specific patterns of genomic instability. Given that cohesin is fundamental to DNA double-strand break repair, its deficiency creates a rationale for exploring synthetic lethality-based therapeutic approaches, particularly PARP inhibitors, in MDS. The evaluation of STAG2 expression by immunohistochemistry is an accessible approach for diagnostic laboratories and may represent a promising complementary biomarker for identifying subsets of MDS patients eligible for HSCT, and especially those not eligible for HSCT, who may benefit from personalized therapeutic strategies. Conclusion: Reduced STAG2 expression occurs in over half of MDS patients and is associated with +8 and complex karyotypes, serving as a potential biomarker and a target for precision medicine via synthetic lethality.
SN  - 2531-1379
SN  - 2531-1387
ER  -