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.

Keywords: Hematology; Thrombocythemia, Essential; Myelofibrosis; Chromosome Aberrations; Mutation; Case Reports