Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia
Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia
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幼年粒单核细胞白血病 KRAS 基因杂合性丢失 (LOH) 谱系依赖性偏斜
DOI：
10.1111/ejh.12355
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发表时间：
2014
期刊：
影响因子：
3.1
通讯作者：
Eguchi M.
中科院分区：
文献类型：
--
作者：
Tokuda K;Eguchi-Ishimae M;Iwabuki H;Kawakami S;Tauchi H;Ishii E;Eguchi M.
幼年型粒单核细胞白血病（JMML）是一种由造血干细胞异常引起的克隆性疾病，尽管在报告的病例中淋巴系的参与有所不同。在这里，我们提出了一个案件的JMML与aKRASG 13 D突变。在各种造血谱系中检测到突变，包括T和B淋巴细胞以及谱系-CD 34 + CD 38-造血干细胞，显示每个谱系中受影响细胞的百分比不同。基于单细胞的造血细胞分析揭示了野生型KRAS在相当大比例的G13 D携带细胞中的丢失。杂合性缺失（洛）/非洛细胞的百分比显示造血细胞中的谱系依赖性偏斜。野生型KRAS等位基因的丢失可能是KRAS相关JMML中常见的继发性遗传变化，并可能影响早期JMML祖细胞的分化行为。
Juvenile myelomonocytic leukemia (JMML) is a clonal disease arising from abnormal hematopoietic stem cells, although the involvement of lymphoid lineage differs among reported cases. Here, we present a case of JMML with aKRASG13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage−CD34+CD38−hematopoietic stem cells, showing a different percentage of affected cells in each lineage. Single cell‐based analysis of hematopoietic cells revealed the loss of wild‐typeKRASin a significant proportion of G13D‐harboring cells. The percentage of loss of heterozygosity (LOH)/non‐LOH cells showed lineage‐dependent skewing in hematopoietic cells. The loss of the wild‐typeKRASallele may be a common secondary genetic change inKRAS‐related JMML and may affect the differentiation behavior of early JMML progenitors.