The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease
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DOI：
10.1182/blood-2005-02-0531
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发表时间：
2005-09-15
期刊：
影响因子：
20.3
通讯作者：
Loh, ML
中科院分区：
文献类型：
--
作者：
Kratz, CP;Niemeyer, CM;Loh, ML
生殖系PTPN11突变导致50％的Noonan综合征病例（NS）。 PTPN11的体细胞突变发生在35％的NOVO，非疾病少年骨髓细胞性白血病（JIMML）的患者中。在NS（NS/MPD）的婴儿中也可能发生骨髓增生性疾病（MPD），即瞬态或更暴发的形式。我们从77例新报告的JMML（n = 69）或NS/MPD（n = 8）的患者（n = 8）中鉴定出血液或骨髓标本中的PTPN11突变。与先前的报道一起，我们比较了3组PTPN11突变的光谱：（1）JMML患者（n = 10）； （2）NS/MPD患者（n = 19）； （3）NS患者（n = 243）。 GLU76是JMML中最常见的残基（n = 45），GLU76LYS的变化（n = 29）最常见。 NS/ MPD的19例患者中有8名携带THR73ILE替代。这些数据表明，在JMML，NS/ MPD和NS的患者中发现的PTPN11突变频谱中存在基因型/势型相关性。这有助于表征NS患者血液学异常的频谱，并更好地定义PTPN11病变对NS/ MPD和JMML患者的疾病病程的影响。
Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JIMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD). We identified PTPN11 mutations in blood or bone marrow specimens from 77 newly reported patients with JMML (n = 69) or NS/MPD (n = 8). Together with previous reports, we compared the spectrum of PTPN11 mutations in 3 groups: (1) patients with JMML (n = 10); (2) patients with NS/MPD (n = 19); and (3) patients with NS (n = 243). Glu76 was the most commonly affected residue in JMML(n = 45), with the Glu76Lys alteration (n = 29) being most frequent. Eight of 19 patients with NS/ MPD carried the Thr73Ile substitution. These data suggest that there is a genotype/pheno type correlation in the spectrum of PTPN11 mutations found in patients with JMML, NS/ MPD, and NS. This supports the need to characterize the spectrum of hematologic abnormalities in individuals with NS and to better define the impact of the PTPN11 lesion on the disease course in patients with NS/ MPD and JMML.