Myelofibrosis in Philadelphia chromosome–negative myeloproliferative neoplasms is associated with aberrant karyotypes

In Philadelphia chromosome–negative myeloproliferative neoplasms (Ph− MPN), non-specific chromosomal defects are detectable and essential thrombocythemia (ET) has the lowest rate of aberrations, whereas primary myelofibrosis (PMF) and post-polycythemia vera (PV) myelofibrosis have the highest rates of aberrations. The frequency of cytogenetic defects in pre-fibrotic stage PMF has not been characterized thus far and the underlying molecular defects of chromosomal instability are unknown. In this study, histopathological findings were correlated with cytogenetic data (n = 249). The expression of DNA repair factors ERCC1 and LIG4 were determined in Ph− MPN with and without cytogenetic aberrations. Pre-fibrotic PMF and ET have similarly low frequencies of karyotype anomalies. The expression of ERCC1, but not LIG4, is increased in fibrotic stage PMF but is not associated with accumulation of cytogenetic defects. In conclusion, aberrant karyotypes in Ph− MPN reflect the chromosomal instability in these diseases and, in comparison with pre-fibrotic stages, Ph− MPN with fibrosis has the highest frequency of cytogenetic aberrations.