Advances in understanding the pathogenesis of familial myeloproliferative neoplasms.

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.

Rumi E ，Cazzola M 《-》

Familial MPN Predisposition.

Tashi T ，Swierczek S ，Prchal JT 《-》

Germline genetic factors in the pathogenesis of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are clonal hematological malignancies that lead to overproduction of mature myeloid cells. They are due to acquired mutations in genes encoding for AK2, MPL and CALR that result in the activation of the cytokine receptor/JAK2 signaling pathway. In addition, it exists germline variants that can favor the initiation of the disease or may affect its phenotype. First, they can be common risk alleles, which correspond to frequent single nucleotide variants present in control population and that contribute to the development of either sporadic or familial MPN. Second, some variants predispose to the onset of MPN with a higher penetrance and lead to familial clustering of MPN. Finally, some extremely rare genetic variants can induce MPN-like hereditary disease. We will review these different subtypes of germline genetic variants and discuss how they impact the initiation and/or development of the MPN disease.

Bellanné-Chantelot C ，Rabadan Moraes G ，Schmaltz-Panneau B ，Marty C ，Vainchenker W ，Plo I ... -  《-》

The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms.

Olcaydu D ，Rumi E ，Harutyunyan A ，Passamonti F ，Pietra D ，Pascutto C ，Berg T ，Jäger R ，Hammond E ，Cazzola M ，Kralovics R ... -  《-》

The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms.

Soler G ，Bernal-Vicente A ，Antón AI ，Torregrosa JM ，Caparrós-Pérez E ，Sánchez-Serrano I ，Martínez-Pérez A ，Sánchez-Vega B ，Vicente V ，Ferrer-Marin F ... -  《-》