Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations
Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations
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DOI：
10.1182/blood-2006-09-046649
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发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Koike, Kenichi
中科院分区：
文献类型：
--
作者：
Matsuda, Kazuyuki;Shimada, Akira;Koike, Kenichi
在11例携带RAS突变（8例NRAS突变，3例KRAS 2突变）的青少年粒单核细胞白血病（JMML）患儿中，5例在诊断时白色血细胞和脾脏大小之一或两者均显著升高。3例患者在就诊时没有或有中度肝脾肿大和轻度白细胞增多，但随后显示脾脏大小显著增加，伴或不伴血液学恶化，因此开始非强化化疗。另外3例NRAS或KRAS 2甘氨酸-丝氨酸置换患者未接受化疗，但在2- 4年随访期间观察到血液学改善。在第三组中，分析的所有造血细胞谱系在血液学改善时具有RAS突变，而从指甲获得的DNA具有野生型。此外，在临床过程中，循环粒细胞-巨噬细胞祖细胞的数量显著减少。因此，一些具有特定RAS突变的JMMIL患者可能具有自发改善的疾病。
Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoletic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMMIL with specific RAS mutations may have spontaneously improving disease.