Hayashi SHIGEFUMI, Iwama HIROSHI, Yahata NAOYUKI, Ando KEIKO, Ohyashiki JUNKO H., Ohyashiki KAZUMA
First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Hematology. 1999;4(1):1-10. doi: 10.1080/10245332.1999.11746425.
Telomeres consist of simple tandem hexametric (TTAGGG) repeats and progressively shorten with cell replication. To determine a relationship between telomeric erosion and response to treatment, we measured telomere length following treatment in patients with chronic myeloid leukemia (CML) in the chronic phase. We used 70 samples of bone marrow mononuclear cells obtained from 26 patients with CML in the chronic phase subsequently. Telomere length was determined by a Southern hybridization of HinfI-digested DNA using a (TTAGGG)(4) probe, and the terminal restriction fragment (TRF) length was measured. Telomerase activity was also measured in 14 CML patients at the time of diagnosis using a telomeric repeat amplification protocol (TRAP) assay. Of the 26 patients with CML at the time of diagnosis, 14 had normal TRF lengths and the remaining 12 had shortened TRFs compared to those of age-matched normal individuals. In a group of CML patients treated with interferon alpha (IFNalpha), 80% of those who showed normal TRFs obtained cytogenetic responses. Approximately 50% of patients with shortened TRFs and treated with IFNalpha showed normalization of TRFs after IFNalpha treatment and all of them were cytogenetic responders. None of the CML patients with shortened TRFs before and after IFNalpha treatment achieved major cytogenetic response and they had high levels of telomerase activity. In the group of CML patients treated with hydroxyurea alone, although some patients showed normalization of TRF lengths after treatment, none of them showed major cytogenetic response. Telomere length before treatment may be related to CML disease severity. Cytogenetic response could be expected in CML patients with normal TRF lengths and treated with IFNalpha. Thus, measurement of telomere length after treatment might provide important information in managing CML patients.
端粒由简单的串联六聚体（TTAGGG）重复序列组成，并随着细胞复制而逐渐缩短。为了确定端粒侵蚀与治疗反应之间的关系，我们在慢性期慢性髓性白血病（CML）患者治疗后测量了端粒长度。随后，我们使用了从26例慢性期CML患者中获取的70份骨髓单个核细胞样本。通过使用（TTAGGG）（4）探针的HinfI消化DNA的Southern杂交来确定端粒长度，并测量末端限制片段（TRF）长度。在诊断时，还使用端粒重复序列扩增协议（TRAP）测定法对14例CML患者的端粒酶活性进行了测量。在诊断时的26例CML患者中，与年龄匹配的正常个体相比，14例患者的TRF长度正常，其余12例患者的TRF缩短。在一组接受α干扰素（IFNα）治疗的CML患者中，TRF正常的患者中有80％获得了细胞遗传学反应。约50％TRF缩短且接受IFNα治疗的患者在IFNα治疗后TRF恢复正常，并且所有这些患者都是细胞遗传学反应者。IFNα治疗前后TRF缩短的CML患者均未达到主要细胞遗传学反应，并且它们具有高水平的端粒酶活性。在仅接受羟基脲治疗的CML患者组中，尽管一些患者治疗后TRF长度恢复正常，但他们均未显示主要细胞遗传学反应。治疗前端粒长度可能与CML疾病严重程度相关。TRF长度正常且接受IFNα治疗的CML患者有望出现细胞遗传学反应。因此，治疗后端粒长度的测量可能为管理CML患者提供重要信息。
