Objective: Myeloproliferative disorders (MPD) are clonal hematopoietic diseases that include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Mutations in JAK2 are present in many MPD patients. Additional genomic abnormalities are not fully examined in MPD.
Materials and methods: We used single-nucleotide polymorphism DNA microarray (SNP-chip) to analyze 43 patients with MPD (10 PV, 17 ET, and 16 PMF) for genomic aberrations.
Results: Genomic abnormalities were rare in ET. The region containing either RB (13q14) or NF1 (17q11) was deleted in 4 of the 16 PMF, especially PMF with no JAK2 mutations. All five cases of PV having homozygous JAK2V617F had loss of heterozygosity with normal copy number [uniparental disomy] involving the gene. A subpopulation with 9p uniparental disomy was detected in 11 MPD (3 PV, 1 ET, 7 PMF). Uniparental disomy at 1p was found in one PV and three PMF. A novel mutation of MPL (Y591D), which was involved in this uniparental disomy, was found in 1 PV with JAK2 mutation. The other three cases of PMF with 1p uniparental disomy had point mutations of the MPL gene, either a novel mutation (S204F) or the previously described W515L.
Conclusion: Genomic abnormalities, including 9p uniparental disomy/JAK2 point mutations, 1p uniparental disomy/MPL point mutations, deletions of RB1 and NF1 are common alterations in MPD, especially in PMF.