Clinical Characteristics and Outcomes of Patients with Primary and Secondary Myelofibrosis According to the Genomic Classification Using Targeted Next-Generation Sequencing

Simple Summary Myelofibrosis is a heterogeneous disease regarding its mutation landscape as well as its clinical presentation and outcome. A genomic classification with prognostic implications of myeloproliferative neoplasms has been previously proposed, however, this classification has hardly been implemented in myelofibrosis. The aim of our work is to evaluate this genomic classification in a large series of myelofibrosis patients from a single institution, taking into account whether cases are primary or secondary. We found that both primary and secondary myelofibrosis have distinctive molecular landscapes and that genomic profiling provides accurate information regarding prognosis and disease progression. Myelofibrosis (MF) is a heterogeneous disease regarding its mutational landscape, clinical presentation, and outcomes. The aim of our work is to evaluate the genomic classification of MF considering whether it is primary or secondary. One-hundred seventy-five patients, 81 with primary MF (PMF) and 94 with secondary MF (SMF) were hierarchically allocated into eight molecular groups. We found that TP53 disruption/aneuploidy (n = 16, 9%) was more frequent (12% versus 6%) and showed higher allele burden (57% versus 15%, p = 0.01) in SMF than in PMF, and was associated with shorter survival (median 3.5 years). Mutations in chromatin/spliceosome genes (n = 72, 41%) represented the most frequent genomic group in PMF. Homozygous JAK2 mutation (n = 40, 23%) was enriched with old patients with SMF after long-standing polycythemia vera, whereas MF with heterozygous JAK2 mutation (n = 22, 13%) was similarly distributed among PMF and SMF. MF with CALR mutation (n = 19, 11%) predominated in post-essential thrombocythemia MF. The remaining genomic groups were infrequent. TP53 disruption, chromatin/spliceosome mutation, and homozygous JAK2 mutation were associated with significantly shorter survival and higher risk of progression. In conclusion, genomic classification reveals different pathogenic pathways between PMF and SMF and provides relevant information regarding disease phenotype and outcomes.

Automated summary

This study aims to evaluate the accuracy and predictive ability of a genomic classification system in different types of myelofibrosis patients. The study found that primary and secondary myelofibrosis have distinct genomic characteristics, and genomic profiling can provide accurate information about prognosis and disease progression.