Pb2208 molecular profile and telomere length are useful markers for differential diagnosis of pre-fibrotic primary myelofibrosis versus essential thrombocythemia

Background: The 2016 revised WHO classification of MPN newly presented pre‐fibrotic PMF. Diagnostic criteria is based on bone marrow morphology, fibrosis, and clinical features (leukoerythroblastosis, anemia, leukocytosis, increased lactate dehydrogenase, and palpable splenomegaly). Since pre‐fibrotic PMF is a new entity characterized by a unique combination of both thrombotic and hemorrhagic risk, a differentiation from essential thrombocythemia (ET) is pivotal for treatment decision. However, the differentiation is difficult in many cases. Aims: In this study, we sought to explore useful markers for the differential diagnosis of ET and pre‐fibrotic PMF. We compared the cytogenetic and molecular profiles, telomere length, survival rate of patients among pre‐fibrotic PMF, overt PMF and ET. Methods: We reviewed BM morphology and clinical data of 59 Korean patients diagnosed with MPN in 2005∼2014. We classified MPN subtypes of them in series of 2001∼2016 WHO criteria. G‐banding/FISH (BCR/ABL1, 20q deletion, 13q deletion) (n = 57), targeted sequencing of 88 genes (n = 59), telomere/centromere ratio using quantitative FISH (n = 44), and survival analysis (n = 59) were performed. Results: Among 15 patients with MPN‐U by WHO 2001∼2014 classification, 7 patients were re‐diagnosed with pre‐fibrotic PMF, 2 with overt PMF, 6 with MPN‐U by WHO 2016 classification. Based on WHO 2016 classification, cytogenetic abnormalities were detected as 0% in ET, 0% in pre‐fibrotic PMF, and 42.3% in overt PMF. The numbers of mutated genes were 1.5 ± 1.3, 2.4 ± 1.3, 2.0 ± 1.2 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.542). The spectrum of mutate genes expanded from ET to overt PMF. Telomere length (telomere/centromere ratio) were 14.5 ± 1.4, 10.1 ± 3.1, 9.2 ± 3.7 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.042). 5‐year survival rates were 100%, 71.4%, 49.5% in ET, pre‐fibrotic PMF, overt PMF, respectively. Summary/Conclusion: Pre‐fibrotic PMF patients were found to harbor more number of mutations than ET. Mutation profile expanded and telomere lengths decreased in order of disease severity. Especially, C SF3R, DNMT3A, SF3B1, SRSF2 mutation can be candidate marker for differential diagnosis between ET and pre‐fibrotic PMF. Telomere length definitely gives information about disease severity, which is a useful indicator in differential diagnosis of MPN. image