According to the new World Health Organization (WHO) classification (2008), chronic myeloid malignancies are divided in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and overlap MDS/MPN cases. From morphological aspects, these categories show overlaps. To evaluate whether these morphological similarities have genetic parallels, we investigated 1,851 cases with suspected/confirmed myelodysplastic or myeloproliferative diseases by chromosome banding and molecular analyses. Cytogenetics revealed aberrant karyotypes in 354 patients (19.1% of the original cohort) who were the basis of further analysis. The distribution of chromosomal aberrations differed significantly between categories. Isolated +9 and gain of 9p were exclusively observed in MPN (+9: 10/93; 11%; p <0.001; +9p: 6/93; 7% of all aberrant MPN cases) but were not detected in MDS or MDS/MPN (p = 0.001). Isolated del(5q) (p = 0.002), -7 in combination with other aberrations (p = 0.016), and complex aberrations (p = 0.003) were 2.9- to 7.5-fold more frequent in MDS than in MPN. Trisomies 8 and 21 and del(20q) were comparably frequent in both subgroups. Interestingly, the MDS/MPN overlap cohort showed a higher frequency of -7 accompanied by other aberrations (3/17; 18% of all aberrant cases; p = 0.001), i(17)(q10) (2/17; 12%; p = 0.013), and +21 (2/17; 12%; p = 0.013) when compared to MPN or MDS only. These differences support the category for MDS/MPN within the new WHO classification. Overlaps between the diverse disorders were seen also for the JAK2V617F (MPN 66/89; 74%; MDS/MPN 4/14; 29%; MDS 2/63; 3%) and NRAS mutations (MDS 2/67; 3%; MPN 2/4; MDS/MPN 1/1). In conclusion, cytogenetics and molecular genetics show overlaps in varying proportions of MDS and MPN cases which might indicate common pathways in their etiology. Some markers are strongly associated with one of these disorders and can be helpful for differential diagnosis especially in difficult cases.
