MOLECULAR GENETICS AND PATHOGENESIS OF CHRONIC MYELOPROLIFERATIVE NEOPLASMS: THE ROLES OF JAK2 V617F, CALR, MPL MUTATIONS, AND THE JAK-STAT PATHWAY
Keywords:
Keywords: Chronic Myeloproliferative Neoplasms, JAK2 V617F, CALR Mutation, MPL Mutation, JAK-STAT Pathway, Molecular Pathogenesis, Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, Targeted Therapy.Abstract
Abstract: Chronic Myeloproliferative Neoplasms (MPNs) are clonal
disorders of hematopoietic stem cells characterized by excessive proliferation of
myeloid lineages. The pathogenesis of these disorders is closely associated with
somatic mutations in genes that control intracellular signaling. Among these, mutations
in JAK2 (V617F), CALR (Calreticulin), and MPL (myeloproliferative leukemia
virus oncogene) are the most commonly implicated in BCR-ABL-negative MPNs.
These mutations result in constitutive activation of the JAK-STAT pathway, leading to
uncontrolled cell growth, survival, and cytokine hypersensitivity. Understanding these
genetic alterations is essential for accurate diagnosis, prognosis, and treatment of
MPNs. This article provides an in-depth review of the genetic mechanisms underlying
MPNs, focusing on the roles of JAK2 V617F, CALR, MPL, and the JAK-STAT
signaling pathway, and highlights current and emerging targeted therapies that are
shaping modern clinical practice.
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