Genomic characterization in triple-negative primary myelofibrosis and other myeloid neoplasms with bone marrow fibrosis
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Triple-negative primary myelofibrosis (TN-PMF) and other myeloid neoplasms with associated bone marrow fibrosis such as the myelodysplastic syndromes (MDS-F) or the myelodysplastic/myeloproliferative neoplasms (MDS/MPN-F) are rare entities, often difficult to distinguish from each other. Thirty-four patients previously diagnosed with TN-PMF (n = 14), MDS-F (n = 18), or MDS/MPN-F (n = 2) were included in the present study. After central revision of the bone marrow histology, diagnoses according to the 2016-WHO classification were TN-PMF (n = 6), MDS-F (n = 19), and MDS/MPN-F (n = 9), with TN-PMF genotype representing only 4% of a cohort of 141 molecularly annotated PMF. Genomic classification according to next-generation sequencing and cytogenetic study was performed in 28 cases. Median number of mutations was 4 (range 1–7) in cases with TP53 disruption/aneuploidy or with chromatin-spliceosome mutations versus 1 mutation (range 0–2) in other molecular subgroups (p < 0.0001). The number of mutations and the molecular classification were better than PMF and MDS conventional scoring systems to predict survival and progression to acute leukemia. In conclusion, TN-PMF is an uncommon entity when the 2016 WHO criteria are strictly applied. Genomic classification may help in the prognostic assessment of patients with myeloid neoplasms with bone marrow fibrosis.
KeywordsPrimary myelofibrosis Myelodysplastic syndromes Diagnosis Prognosis Genomic classification
This work was supported by the grant PI18/00205 from the Instituto de Salud Carlos III (ISCIII), through the Plan Estatal de Investigación Científica y Técnica y de Innovación and 2017 SGR 1655. This work was co-funded by the European Regional Development Fund (ERDF). We are indebted to the genomics Core facility of the IDIBAPS for the technical help.
AAL designed the study, collected the data, performed the statistical analysis, analyzed and interpreted the results, and wrote the paper. MLG and DC performed the molecular studies, interpreted the results, and wrote the paper. DM and MR reviewed the bone marrow biopsies, interpreted the results, and wrote the paper. JGC, IM, and MT collected the data and approved the final version. JCHB, JE, and FC collected the data, interpreted the results, and wrote the paper.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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