{"id":246912,"date":"2026-11-09T06:17:03","date_gmt":"2026-11-09T12:17:03","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/11\/the-jak2-v617f-revolution-in-myeloproliferative-neoplasms"},"modified":"2026-11-09T06:17:03","modified_gmt":"2026-11-09T12:17:03","slug":"the-jak2-v617f-revolution-in-myeloproliferative-neoplasms","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/11\/the-jak2-v617f-revolution-in-myeloproliferative-neoplasms","title":{"rendered":"The JAK2 V617F revolution in myeloproliferative neoplasms"},"content":{"rendered":"\n<p>1951, William Dameshek (1900\u22121969) penned an editorial in <i>Blood<\/i> highlighting shared phenotype (i.e., trilineage proliferation, splenomegaly, bone marrow fibrosis) among the myeloproliferative and related myeloid neoplasms, including chronic myeloid leukemia (CML; then referred to as \u201cchronic granulocytic leukemia\u201d), polycythemia vera (PV), essential thrombocythemia (ET; then referred to as \u201cmegakaryocytic leukemia\u201d), and primary myelofibrosis (PMF; then referred to as \u201cidiopathic or agnogenic myeloid metaplasia of spleen\u201d).<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/14505#ref1\">1<\/a><\/sup> He also discussed transitional (e.g., post-PV myelofibrosis) and pre-fibrotic states and contended that these \u201cmyeloproliferative disorders\u201d were closely interrelated and represented variable manifestations of a constitutively-driven bone marrow proliferative activity arising from a \u201chitherto undiscovered stimulus\u201d.<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/14505#ref1\">1<\/a><\/sup><\/p>\n<p>In 1960, Nowell and Hungerford described the Philadelphia chromosome that ultimately led to the identification of BCR::ABL1 as the disease-causing mutation in CML and the successful launching of imatinib (ABL tyrosine kinase inhibitor) as a disease-modifying drug therapy. By contrast, the molecular basis of PV, ET, and PMF remained elusive until the March, 2005 breakthrough communication by James et al., describing a novel Janus kinase 2 JAK\/STAT activating mutation (JAK2V617F located in the auto-inhibitory JH2 pseudo-kinase domain \u2014 a G to T somatic mutation at nucleotide 1849, in exon 14, resulting in the substitution of valine to phenylalanine at codon 617) in PV, ET and PMF (discovery patent filing in October 2004).<sup>2<\/sup> The authors utilized short interfering RNA to knock down JAK2 expression and demonstrated the essential role of JAK2 in erythropoietin-independent growth in PV (Figure 1).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>1951, William Dameshek (1900\u22121969) penned an editorial in Blood highlighting shared phenotype (i.e., trilineage proliferation, splenomegaly, bone marrow fibrosis) among the myeloproliferative and related myeloid neoplasms, including chronic myeloid leukemia (CML; then referred to as \u201cchronic granulocytic leukemia\u201d), polycythemia vera (PV), essential thrombocythemia (ET; then referred to as \u201cmegakaryocytic leukemia\u201d), and primary myelofibrosis (PMF; then [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,1522],"tags":[],"class_list":["post-246912","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-innovation"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/246912","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=246912"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/246912\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=246912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=246912"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=246912"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}