Fig. 4: A proposed conceptual framework of myelofibrosis genetic etiology.
From: Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis
Both longer inherited telomere length and the germline JAK2 risk haplotype tagged by rs7851556 are associated with increased risk of myelofibrosis. The germline JAK2 risk haplotype further predisposes to somatically acquire the JAK2V617F mutation in cis, and mosaic chromosomal alterations in the 9p24.1 region lead to over-representation of the germline risk haplotype and JAK2V617F somatic mutation. We hypothesize that increasing JAK2 activity underlies each of these processes which leads to increased clonal expansion and proliferation, and accelerated telomere length shortening in myelofibrosis patients.
