Clonal Evolution of CALR-Mutated Essential Thrombocythemia With Chromosome 1q Jumping Translocations: A Rare Case Report

Objective:Rare disease Background:Essential thrombocythemia (ET), a chronic myeloproliferative neoplasm, typically follows an indolent clinical course; however, some patients may undergo clonal evolution to post-ET myelofibrosis or leukemic transformation.Disease progression is frequently associated with acquisition of additional cytogenetic and molecular abnormalities, although the precise molecular mechanisms underlying this evolution remain incompletely understood.We describe a case of post-ET myelofibrosis arising from calreticulin (CALR)-mutated ET associated with gain of chromosome 1q21, chromosome 1q jumping translocations, and a BRIP1 gene mutation. Case Report:We report a 77-year-old man with CALR-mutated ET diagnosed in 2007 and treated with long-term hydroxyurea.After 18 years, he developed progressive anemia, circulating blasts, and splenomegaly.Bone marrow biopsy demonstrated marked hypercellularity (~ 95% cellularity) with myeloid and megakaryocytic hyperplasia, megakaryocytic atypia, and loose clustering, along with severe reticulin fibrosis (MF-3, myelofibrosis tier 3, WHO grade system) and increased blasts (5%-8% by CD34 immunohistochemistry).Next-generation sequencing (163-gene/40-fusion panel) confirmed CALR p.L367Tfs46 mutation persistence and BRIP1 p.R798* nonsense mutation acquisition.Fluorescence in situ hybridization showed gain of chromosome 1q21.Cytogenetics demonstrated jumping translocations of 1q involving chromosomes 14, 16, and 22. Conclusions:This report describes the case of a patient with an 18-year history of CALR-mutated ET, presenting with leukocytosis, anemia, marked thrombocytosis, splenomegaly, severe myelofibrosis, and acquisition of a BRIP1 p.R798 mutation, gain of chromosome 1q21, and jumping translocations of the long arm of chromosome 1 (1q) involving recipient chromosomes 14, 16, and 22.This case illustrates late clonal evolution of CALR-mutated ET to post-ET myelofibrosis associated with rare cytogenetic and molecular abnormalities.These findings expand the spectrum of genetic events observed during this disease progression.