FMS MUTATIONS IN MYELODYSPLASTIC, LEUKEMIC, AND NORMAL SUBJECTS
FMS MUTATIONS IN MYELODYSPLASTIC, LEUKEMIC, AND NORMAL SUBJECTS
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DOI：
10.1073/pnas.87.4.1377
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发表时间：
1990-02-01
影响因子：
11.1
通讯作者：
PADUA, RA
中科院分区：
文献类型：
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作者：
RIDGE, SA;WORWOOD, M;PADUA, RA
FMS基因编码集落刺激因子1（巨噬细胞和单核细胞特异性生长因子）的功能性细胞表面受体。密码子969和301已被鉴定为可能参与促进FMS的转化活性。密码子301处的突变被认为通过受体的配体独立性和组成型酪氨酸激酶活性导致肿瘤转化。密码子969处的酪氨酸残基已被证明参与负调节活性，其被氨基酸取代破坏。本研究报告的频率点突变在这些密码子，在体内，在人类骨髓恶性肿瘤和正常受试者。我们研究了110例患者[67例骨髓增生异常（MDS）和48例急性髓细胞白血病（AML）]，5例患者正在研究的MDS和晚期AML阶段的疾病。969位密码子突变总发生率为12.7%（14/110），301位密码子突变总发生率为1.8%（2/110）。两名患者在疾病的AML阶段有突变，但在先前的MDS中没有，一名患者在MDS阶段有突变，但在AML转化时没有。这与这些突变的体细胞起源一致。FMS突变在慢性粒单核细胞白血病和AML M4型（23%）中最常见（20%），这两种疾病的特征均为单核细胞分化。51例正常受试者中有1例存在构成密码子969突变，这可能是骨髓恶性肿瘤易感性的标志。
The FMS gene encodes the functional cell surface receptor for colony-stimulating factor 1, the macrophage- and monocyte-specific growth factor. Codons 969 and 301 have been idntified as potentially involved in promoting the transforming activity of FMS. Mutations at codon 301 are believed to lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. The tyrosine residue at codon 969 has been shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. This study reports on the frequency of point mutations at these codons, in vivo, in human myeloid malignancies and in normal subjects. We studied 110 patients [67 with myelodysplasia (MDS) and 48 with acute myeloblastic leukemia (AML)], 5 patients being studied at the MDS and the later AML stage of the disease. There was a total incidence of 12.7% (14/110) with mutations in codon 969 and 1.8% (2/110) with mutations in codon 301. Two patients had mutations in the AML stage of the disease but not in the preceding MDS and one had a mutation in the MDS stage but not upon transformation of AML. This is consistent with the somatic origin of these mutations. FMS mutations were most prevalent (20%) in chronic myelomonocytic leukemia and AML type M4 (23%), both of which are characterized by monocytic differentiation. One of 51 normal subjects had a constitutional codon 969 mutation, which may represent a marker for predisposition to myeloid malignancy.