13 , 14 , 15 Genome-wide association studies in JAK2 V617F -positive clonal hematopoiesis (CH) or myeloproliferative neoplasm (MPN) show highly significant associations with loci in JAK2, TERT, SH2B3, TET2, ATM, CHEK2, PINT , and GFIB , with nearly 18% of heritable risk attributed to these and other loci. 16 , 17 , 18 Inflammatory states and/or genetic predisposition to inflammation are risk factors for both the acquisition and expansion of JAK2 V617F clones, as is male sex. 10 , 19 , 20 , 21 , 22 , 23 , 24 JAK2 V617F VAF in HSC and terminally differentiated blood cell pathophysiology JAK2 V617F increases signal transduction and drives quantitative and qualitative alterations in HSC biology.
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