Ventura Ferreira Mónica S, Crysandt Martina, Ziegler Patrick, Hummel Sebastian, Wilop Stefan, Kirschner Martin, Schemionek Mirle, Jost Edgar, Wagner Wolfgang, Brümmendorf Tim H, Beier Fabian
Department of Hematology, Oncology, Haemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany.
Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany.
Ann Hematol. 2017 Sep;96(9):1457-1461. doi: 10.1007/s00277-017-3049-z. Epub 2017 Jul 3.
Telomere shortening represents an established mechanism connecting aging and cancer development. We sequentially analyzed telomere length (TL) of 49 acute myeloid leukemia (AML) patients at diagnosis (n = 24), once they achieved complete cytological remission (CCR) and/or during refractory disease or relapse and after 1-year follow-up, with all patients having at least two sequential samples. TL was analyzed by monochrome multiplex quantitative polymerase chain reaction. We have observed substantially shortened TL in the cells of patients at diagnosis compared to age-adjusted controls. In patients reaching CCR after chemotherapy, telomere shortening was less pronounced than in persistence or relapse but still significantly shortened compared to controls. We estimate patients harboring approximately 20 years of premature telomere loss compared to healthy aged-matched subjects at the time of AML onset. Our data indicate a pre-existing telomere deficit in non-clonal hematopoiesis of AML patients providing a link between age and AML development.
端粒缩短是一种将衰老与癌症发展联系起来的既定机制。我们对49例急性髓系白血病（AML）患者在诊断时（n = 24）、达到完全细胞学缓解（CCR）时和/或难治性疾病或复发期间以及1年随访后进行了端粒长度（TL）的序贯分析，所有患者至少有两个序贯样本。通过单色多重定量聚合酶链反应分析TL。我们观察到，与年龄调整后的对照组相比，诊断时患者细胞中的TL显著缩短。化疗后达到CCR的患者，端粒缩短不如持续或复发时明显，但与对照组相比仍显著缩短。我们估计，与健康的年龄匹配受试者相比，AML发病时患者的端粒提前丢失约20年。我们的数据表明，AML患者的非克隆造血中存在预先存在的端粒缺陷，这为年龄与AML发展之间提供了联系。
