International journal of molecular sciences 2018 04 1119(4) pii 10.3390/ijms19041152
The germline haplotype known as "GGCC or 46/1 haplotype" (haplotype) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the intron 10 to the Insulin-like 4 () gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a "GGCC" combination are more frequently indicated to represent the haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both V617 and exon 12 mutations. The association between the haplotype and mutations in other genes, such as thrombopoietin receptor () and calreticulin (), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the haplotype in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the haplotype and blood cell count, survival, or disease progression.