Hematology Department, Hôpital Cochin (APHP), Paris, France.
Haematologica. 2009 Dec;94(12):1676-81. doi: 10.3324/haematol.2009.011205. Epub 2009 Oct 1.
Acquired somatic deletions and loss-of-function mutations in one or several codons of the TET2 (Ten-Eleven Translocation-2) gene were recently identified in hematopoietic cells from patients with myeloid malignancies, including myeloproliferative disorders and myelodys-plastic syndromes. The present study was designed to determine the prevalence of TET2 gene alterations in chronic myelomonocytic leukemias.
Blood and bone marrow cells were collected from 88 patients with chronic phase chronic myelomonocytic leukemia and from 14 with acute transformation of a previously identified disease. Polymerase chain reaction analysis and direct sequencing were used to sequence exons 3 to 11 of the TET2 gene. Annotated single nucleotide polymorphisms were excluded. Survival curves were constructed by the Kaplan-Meier method.
We detected TET2 mutations in 44 of 88 (50%) patients with chronic myelomonocytic leukemia, which suggests that TET2 gene mutations are especially frequent in this myeloid disease. A TET2 gene alteration was identified in 18 of the 43 patients studied at diagnosis and was associated with a trend to a lower overall survival rate; confining the analysis to the 29 patients with chronic myelomonocytic leukemia-1, according to the WHO classification, the difference in overall survival between patients with or without TET2 gene mutations became statistically significant.
TET2 gene alterations are more frequent in chronic myelomonocytic leukemia than in other subgroups of hematopoietic diseases studied so far and could negatively affect the patients' outcome. The striking association between TET2 gene alterations and monocytosis, already observed in patients with systemic mastocytosis, could indicate a negative role of TET2 in the control of monocytic lineage determination.
在患有髓系恶性肿瘤（包括骨髓增生异常综合征和骨髓增殖性疾病）的患者的造血细胞中，最近发现了 TET2（Ten-Eleven Translocation-2）基因的一个或几个密码子的获得性体细胞缺失和功能丧失突变。本研究旨在确定 TET2 基因改变在慢性粒单核细胞白血病中的发生率。
收集 88 例慢性期慢性粒单核细胞白血病患者和 14 例先前确诊疾病急性转化的患者的血液和骨髓细胞。使用聚合酶链反应分析和直接测序对 TET2 基因的外显子 3 至 11 进行测序。排除注释的单核苷酸多态性。通过 Kaplan-Meier 方法构建生存曲线。
我们在 88 例慢性粒单核细胞白血病患者中检测到 44 例（50%）存在 TET2 突变，这表明 TET2 基因突变在这种髓系疾病中尤其常见。在 43 例研究的患者中，有 18 例在诊断时发现 TET2 基因改变，且与总生存率呈下降趋势相关；将分析限定在根据世界卫生组织分类的 29 例慢性粒单核细胞白血病患者中，具有或不具有 TET2 基因突变的患者的总生存率之间的差异具有统计学意义。
与迄今为止研究的其他造血疾病亚组相比，TET2 基因突变在慢性粒单核细胞白血病中更为常见，并且可能对患者的预后产生负面影响。TET2 基因突变与单核细胞增多症之间已经在系统性肥大细胞增多症患者中观察到的显著关联，可能表明 TET2 在单核细胞系确定中的负调控作用。
