02008nam a2200253   4500001000800000005001700008007000300025008004100028040000800069041000800077100003300085245003300118300002300151520125800174650001901432650003901451650003501490650002001525650001901545700003301564773010901597942003101706999001701737ESSALUD20260821144938.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aPlo, Isabelle eAutor954275  aMyeloproliferative neoplasms  apáginas: 788-802  aClassic myeloproliferative neoplasms, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are chronic, clonal hematopoietic stem-cell disorders. These disorders are driven by gain-of-function mutations in the genes Janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL) that activate cytokine signaling. These mutations arise decades before clinical disease develops and confer a clonal advantage that is further shaped by comutations in epigenetic, splicing, or signaling genes. Inflammation enhances clonal dominance, favoring the development of myelofibrosis and thrombotic complications. Disease evolution may culminate in secondary acute myeloid leukemia, which has a poor prognosis. Current therapies primarily aim to control symptoms, thrombosis, and splenomegaly, but they have limited disease-modifying effects, except for pegylated interferon alfa and JAK2 inhibitors in some patients. Emerging therapies that selectively target mutant CALR and JAK2 V617F using immunotherapy and selective inhibitors could be a breakthrough in the treatment of persons with myeloproliferative neoplasms, with the expectation of achieving durable disease modification and potentially clonal eradication.  aCÁNCER91231  aTRATAMIENTOS EN ONCOLOGÍA953734  aENFERMEDAD INFLAMATORIA953667  aLEUCEMIA933873  aLINFOMA939360  aVainchenker, William 9542760 022717922650dMassachusetts NEJM GroupoNEJM12tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-08-21zsqb  c22856d22856