Abstract
The JAK2 46/1 ("GGCC") haplotype is an inherited genetic variation within the Jak2 gene locus that has become a focal point in research related to oncogenesis, particularly in myeloproliferative neoplasms (MPNs). We conducted a narrative review of landmark discoveries in hematological malignancies and Jak2, focusing on its role in oncogenesis, risk stratification, and drug resistance in MPNs. This haplotype spans several polymorphisms within the Jak2 gene. It has been found to increase susceptibility to a variety of hematologic cancers, especially when linked with the somatic JAK2 V617F mutation, which results in the alteration of the JAK/STAT pathway, which is particularly essential for hematopoiesis. The "GGCC" part is characterized by four SNPs, with the G allele of the rs10974944 SNP in this haplotype correlated with MPNs progressing to myelofibrosis. Moreover, the G allele seems to be crucial for the predisposition to onco-drug resistance onset. To conclude, identifying the 46/1 haplotype in patients may not only enhance risk stratification for JAK2-driven cancers but also guide more effective, personalized therapeutic strategies to overcome resistance. Thus, this review aims to describe current knowledge about the JAK2 46/1 haplotype as a marker for diagnosis and the prediction of disease outcome.