Thomas X, Teillon M H, Belhabri A, Rimokh R, Fiere D, Magaud J P, Archimbaud E
Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
Hematol Cell Ther. 1999 Feb;41(1):19-26. doi: 10.1007/s00282-999-0019-5.
Hypermethylation of the calcitonin gene has been described in various hematologic malignancies. In order to assess its frequency and potential usefulness as a marker for leukemic cells and to detect potential clinical correlations, 180 adult patients (aged > 15 years) with newly diagnosed acute leukemia including 133 cases of acute myeloid leukemia (AML) and 47 cases of acute lymphoblastic leukemia (ALL) were tested for its presence in leukemic blasts at diagnosis by Southern blot technique and polymerase chain reaction (PCR) using 3 sets of primers (P550, P566, P1400), amplifying the most frequent sites of hypermethylation upstream or within the gene. In AML, 92 patients (69%) had hypermethylation detected by Southern blot at diagnosis. This hypermethylation could be confirmed by PCR in 18 of 36 tested cases (50%). Hypermethylation was not significantly associated to any clinical or hematological characteristic of the disease. In ALL, 44 patients (94%) had hypermethylation detected by Southern blot at diagnosis. This hypermethylation could be confirmed by PCR in 33 of the 43 tested cases (77%). Sensitivity of PCR assessed by dilution was 1 to 0.1%. Hypermethylation was not either significantly related to any clinical or hematologic characteristics of the disease. Seven ALL cases which were positive by PCR at diagnosis and achieved cytological CR could be tested during CR. Five cases were negative and did not relapse after 3 to 27 months in CR. One case was positive at the beginning of CR and became negative after autologous transplant. However, he relapsed after 9 months in CR, 3 months after the last negative test. PCR for Bcr/Abl was also negative at this time. We conclude that hypermethylation of the calcitonine gene is frequent at diagnosis in adult acute leukemia, particularly in ALL.
降钙素基因的高甲基化已在多种血液系统恶性肿瘤中被描述。为了评估其频率以及作为白血病细胞标志物的潜在用途，并检测潜在的临床相关性，对180例新诊断的成年急性白血病患者（年龄>15岁）进行了检测，其中包括133例急性髓系白血病（AML）和47例急性淋巴细胞白血病（ALL），在诊断时通过Southern印迹技术和聚合酶链反应（PCR），使用3组引物（P550、P566、P1400）检测白血病原始细胞中该基因的存在，这些引物可扩增该基因上游或基因内最常见的高甲基化位点。在AML中，92例患者（69%）在诊断时通过Southern印迹检测到高甲基化。在36例检测病例中的18例（50%）中，这种高甲基化可通过PCR得到证实。高甲基化与该疾病的任何临床或血液学特征均无显著相关性。在ALL中，44例患者（94%）在诊断时通过Southern印迹检测到高甲基化。在43例检测病例中的33例（77%）中，这种高甲基化可通过PCR得到证实。通过稀释评估的PCR敏感性为1至0.1%。高甲基化也与该疾病的任何临床或血液学特征均无显著相关性。7例在诊断时PCR呈阳性且达到细胞学完全缓解（CR）的ALL病例在CR期间可进行检测。5例为阴性，在CR期3至27个月后未复发。1例在CR开始时呈阳性，自体移植后变为阴性。然而，他在CR期9个月后复发，即最后一次阴性检测后3个月复发。此时Bcr/Abl的PCR检测也为阴性。我们得出结论，降钙素基因的高甲基化在成年急性白血病诊断时很常见，尤其是在ALL中。
