Kralovics Robert, Stockton David W, Prchal Josef T
Department of Research, Experimental Hematology, Basel University Hospital, Switzerland.
Blood. 2003 Nov 15;102(10):3793-6. doi: 10.1182/blood-2003-03-0885. Epub 2003 Jun 26.
Familial clustering of malignancies provides a unique opportunity to identify molecular causes of cancer. Polycythemia vera (PV) is a myeloproliferative disorder due to an unknown somatic stem cell defect that leads to clonal myeloid hyperproliferation. We studied 6 families with PV. The familial predisposition to PV appears to follow an autosomal dominant inheritance pattern with incomplete penetrance. All examined females informative for a transcriptional clonality assay had clonal hematopoiesis. We excluded linkage between PV and a number of previously proposed candidate disease loci (c-mpl, EPOR, 20q, 13q, 5q, 9p). Therefore, mutations at these loci are unlikely primary causes of familial PV. The finding of erythropoietin-independent erythroid progenitors in healthy family members indicated the presence of the PV stem cell clone in their hematopoiesis. This finding, together with clonal hematopoiesis in the affected individuals, supports the hypothesis of multiple genetic defects involved in the early pathogenesis of PV.
恶性肿瘤的家族聚集现象为确定癌症的分子病因提供了独特的机会。真性红细胞增多症（PV）是一种骨髓增殖性疾病，由未知的体细胞干细胞缺陷导致克隆性髓系过度增殖引起。我们研究了6个患有PV的家族。PV的家族易感性似乎遵循常染色体显性遗传模式且具有不完全外显率。所有接受转录克隆性检测的信息充分的女性都存在克隆性造血。我们排除了PV与一些先前提出的候选疾病基因座（c-mpl、EPOR、20q、13q、5q、9p）之间的连锁关系。因此，这些基因座的突变不太可能是家族性PV的主要病因。在健康家庭成员中发现不依赖促红细胞生成素的红系祖细胞，表明其造血过程中存在PV干细胞克隆。这一发现，连同受影响个体中的克隆性造血，支持了PV早期发病机制涉及多种遗传缺陷的假说。
