Taketani Takeshi, Taki Tomohiko, Takita Junko, Tsuchida Masahiro, Hanada Ryoji, Hongo Teruaki, Kaneko Takashi, Manabe Atsushi, Ida Kohmei, Hayashi Yasuhide
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Genes Chromosomes Cancer. 2003 Sep;38(1):1-7. doi: 10.1002/gcc.10246.
AML1/RUNX1, located on chromosome band 21q22, is one of the most important hematopoietic transcription factors. AML1 is frequently affected in leukemia and myelodysplastic syndrome with 21q22 translocations. Recently, AML1 mutations were found in adult hematologic malignancies, especially acute myeloid leukemia (AML)-M0 or leukemia with acquired trisomy 21, and familial platelet disorder with a predisposition toward AML. Through the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we examined the AML1 gene for mutations in 241 patients with pediatric hematologic malignancies, and we detected AML1 mutations in seven patients (2.9%). Deletion was found in one patient, and point mutations in four patients, including three missense mutations, two silent mutations, and one mutation within an intron resulting in an abnormal splice acceptor site. All of the mutations except for one were heterozygous. Mutations within the runt domain were found in six of seven patients. Six of seven patients with AML1 mutations were diagnosed with AML, and one had acute lymphoblastic leukemia. In three of these seven patients, AML evolved from other hematologic disorders. AML1 mutations were found in two of four AML-M0 and two of three patients with acquired trisomy 21. Patients with AML1 mutations tended to be older children. Three of four patients with AML1 mutations who received stem cell transplantation (SCT) are alive, whereas the remaining three patients with mutations without SCT died. These results suggest that AML1 mutations in pediatric hematologic malignancies are infrequent, but are possibly related to AML-M0, acquired trisomy 21, and leukemic transformation. These patients may have a poor clinical outcome.
位于21号染色体21q22带的AML1/RUNX1是最重要的造血转录因子之一。在伴有21q22易位的白血病和骨髓增生异常综合征中，AML1经常受到影响。最近，在成人血液系统恶性肿瘤中发现了AML1突变，尤其是急性髓系白血病（AML）-M0或获得性21三体白血病，以及易患AML的家族性血小板疾病。通过聚合酶链反应-单链构象多态性分析，我们检测了241例儿童血液系统恶性肿瘤患者的AML1基因是否存在突变，结果在7例患者（2.9%）中检测到AML1突变。1例患者存在缺失，4例患者存在点突变，其中包括3个错义突变、2个沉默突变和1个内含子内导致异常剪接受体位点的突变。除1例突变外，其余均为杂合突变。7例患者中有6例在 runt 结构域内发现突变。7例AML1突变患者中有6例被诊断为AML，1例患有急性淋巴细胞白血病。在这7例患者中，有3例AML由其他血液系统疾病演变而来。在4例AML-M0患者中有2例以及3例获得性21三体患者中有2例发现了AML1突变。AML1突变的患者往往是年龄较大的儿童。4例接受干细胞移植（SCT）的AML1突变患者中有3例存活，而其余3例未接受SCT的突变患者死亡。这些结果表明，儿童血液系统恶性肿瘤中的AML1突变并不常见，但可能与AML-M0、获得性21三体和白血病转化有关。这些患者的临床预后可能较差。
