Rumi Elisa, Cazzola Mario
Department of Haematology Oncology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Br J Haematol. 2017 Sep;178(5):689-698. doi: 10.1111/bjh.14713. Epub 2017 Apr 25.
Myeloproliferative neoplasms (MPNs) are generally acquired as a result of a somatic stem cell mutation leading to clonal expansion of myeloid precursors. In addition to sporadic cases, familial MPN occurs when one or several MPN affect different relatives of the same family. MPN driver mutations (JAK2, CALR, MPL) are somatically acquired also in familial cases, so a genetic predisposition to acquire one of the MPN driver mutations would be inherited, even though the causative germline mutations underlying familial MPN remain largely unknown. Recently some germline variants [ATG2B and GSKIP duplication, RBBP6 mutations, SH2B3 (LNK) mutations], which can cause familial MPN, have been reported but these mutations are rare and do not explain most familial cases. Patients with familial MPN show the same clinical features and suffer the same complications as those with sporadic disease. This review aims to offer up-to-date information regarding the genetics of familial MPN.
骨髓增殖性肿瘤（MPNs）通常是由于体细胞干细胞突变导致髓系前体细胞克隆性扩增而获得的。除了散发病例外，当一个或多个MPN影响同一家族的不同亲属时，就会发生家族性MPN。在家族性病例中，MPN驱动基因突变（JAK2、CALR、MPL）也是体细胞获得的，因此，即使家族性MPN潜在的致病种系突变在很大程度上仍不清楚，但获得其中一种MPN驱动基因突变的遗传易感性是可遗传的。最近，一些可导致家族性MPN的种系变异（ATG2B和GSKIP重复、RBBP6突变、SH2B3（LNK）突变）已被报道，但这些突变很罕见，无法解释大多数家族性病例。家族性MPN患者与散发性疾病患者表现出相同的临床特征，并遭受相同的并发症。本综述旨在提供有关家族性MPN遗传学的最新信息。
