Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124 Bari, Italy.
Int J Mol Sci. 2018 Apr 11;19(4):1152. doi: 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.
“GGCC 或 46/1 单体型”（单体型）是一种已知的种系单体型，由大约 250kb 区域内的单核苷酸多态性（SNP）组合而成，从内含子 10 延伸到胰岛素样 4（）基因。四个主要的 SNP（rs3780367、rs10974944、rs12343867 和 rs1159782）产生了更频繁表示为“GGCC”组合的单体型。这些 SNP 一起遗传，并且经常与 V617 和外显子 12 突变均为阳性的骨髓增殖性肿瘤（MPN）的发生相关。单体型与其他基因（如血小板生成素受体（）和钙网蛋白（））中的突变之间的关联，或与三阴性 MPN 的关联，仍然存在争议。这篇综述概述了单体型在不同髓系肿瘤发病机制中的频率和作用，并描述了与基因突变相关的假设机制。此外，还讨论了可能的临床意义，因为不同的论文报告了关于单体型与血细胞计数、生存或疾病进展之间相关性的相互矛盾的数据。
