Feraille Aurélie, Etancelin Pascaline, Troche Shirley, Jardin Fabrice, Buchbinder Nimrod, Schneider Pascale, Dugay Magali, Rives Nathalie, Rondanino Christine, Dumont Ludovic
Biology of Reproduction-CECOS Laboratory, Rouen University Hospital, Team "Adrenal and Gonadal Pathophysiology", NorDIC, Inserm U1239, Univ Rouen Normandie, Rouen, France.
Department of Genetic Oncology, Centre Henri Becquerel, Rouen, France.
Hum Reprod. 2025 Aug 1;40(8):1476-1484. doi: 10.1093/humrep/deaf093.
Is it feasible to detect minimal residual disease (MRD) in cryopreserved testicular tissue (TT) from (pre)pubertal boys diagnosed with acute leukemia using molecular biology techniques?
This pilot study demonstrates the feasibility of detecting MRD in cryopreserved TT, which could guide the choice of the safest techniques for fertility restoration.
Fertility preservation through testicular tissue freezing (TTF) is offered to (pre)pubertal boys undergoing highly gonadotoxic treatment. However, the risk of reintroducing leukemic cells during fertility restoration has not been adequately addressed. To date, no study has evaluated the feasibility of detecting residual disease using molecular biology within cryopreserved, thawed and unfixed TT.
STUDY DESIGN, SIZE, DURATION: This pilot study analyzed cryopreserved TT from 14 (pre)pubertal boys diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) who had already received first-line chemotherapy and underwent TTF before hematopoietic stem cell transplantation.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cryopreserved TT from 14 (pre)pubertal boys. Molecular biology techniques, including RT-qPCR and qPCR, were used to detect oncogenic fusion genes or clonal rearrangements of immunoglobulin genes or T-cell receptor (Ig/TCR) in cryopreserved TT samples.
MRD was identified in 36% (5 out of 14) of TT samples using molecular biology techniques. A 21% discordance was observed between conventional histopathology and molecular detection, with molecular methods showing higher sensitivity. No significant association was found between clinical or histological characteristics and MRD status in the TT.
LIMITATIONS, REASONS FOR CAUTION: This study is a pilot study with a small sample size of TT samples from patients with ALL or AML, which may limit the generalizability of the findings. Further studies with larger cohorts are needed to validate our data.
The detection of MRD in cryopreserved TT using molecular biology techniques could help guide the selection of the safest fertility restoration strategies for leukemic patients by minimizing the risk of reintroducing malignant cells. This approach underscores the importance of cryopreserving TT after complete remission of acute leukemia (AL).
STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rouen University Hospital, GIRCI NO, French Biomedicine Agency, and Ligue National Contre le Cancer. The authors declare no competing interests.
Not applicable.
使用分子生物学技术检测已诊断为急性白血病的青春期前男孩的冷冻保存睾丸组织（TT）中的微小残留病（MRD）是否可行？
这项初步研究证明了在冷冻保存的TT中检测MRD的可行性，这可以指导选择最安全的生育力恢复技术。
对于接受高性腺毒性治疗的青春期前男孩，提供通过冷冻睾丸组织（TTF）来保存生育力的方法。然而，在生育力恢复过程中重新引入白血病细胞的风险尚未得到充分解决。迄今为止，尚无研究评估在冷冻保存、解冻且未固定的TT中使用分子生物学检测残留疾病的可行性。
研究设计、规模、持续时间：这项初步研究分析了14名已诊断为急性淋巴细胞白血病（ALL）或急性髓细胞白血病（AML）的青春期前男孩的冷冻保存TT，这些男孩已经接受了一线化疗，并在造血干细胞移植前接受了TTF。
参与者/材料、设置、方法：该研究包括14名青春期前男孩的冷冻保存TT。使用分子生物学技术，包括逆转录定量聚合酶链反应（RT-qPCR）和定量聚合酶链反应（qPCR），来检测冷冻保存TT样本中的致癌融合基因或免疫球蛋白基因或T细胞受体（Ig/TCR）的克隆重排。
使用分子生物学技术在36%（14个样本中的5个）的TT样本中检测到了MRD。在传统组织病理学和分子检测之间观察到21%的不一致性，分子方法显示出更高的敏感性。在TT的临床或组织学特征与MRD状态之间未发现显著关联。
局限性、谨慎原因：本研究是一项初步研究，ALL或AML患者的TT样本量较小，这可能会限制研究结果的普遍性。需要进一步进行更大样本量的研究来验证我们的数据。
使用分子生物学技术在冷冻保存的TT中检测MRD有助于通过将重新引入恶性细胞的风险降至最低，为白血病患者指导选择最安全的生育力恢复策略。这种方法强调了急性白血病（AL）完全缓解后冷冻保存TT的重要性。
研究资金/利益冲突：该研究由鲁昂大学医院、GIRCI NO、法国生物医学机构和法国国家抗癌联盟资助。作者声明无利益冲突。
不适用。
