Genetic Profiling of Myeloproliferative Disorders by Single Nucleotide Polymorphism Oligonucleotide Microarray.

Myeloproliferative disorders (MPD) are clonal hematopoietic diseases including polycythemia vera (PV), essential thrombocytosis (ET) and myelofibrosis with myeloid metaplasia (MMM). Single-nucleotide polymorphism DNA microarray (SNP-Chip) was used to analyze 43 MPDs. All five cases of PV having homozygous JAK2V617F had uniparental disomy (UPD), thus duplicating the allele with the mutated JAK2 and eliminateing the normal allele. Concerning MMM, either the Rb1 (13q14) or NF1 (17q11) gene was deleted in five of the 9 cases that had no Jak2 mutations. Two of these cases had UPD at 1p. Sequencing of the target genes within this region of UPD revealed a point mutation of the MPL gene (S240F or W515L). Each of these cases also had a deletion of Rb suggesting that the mutated MPL may co-operate with an aberrant Rb. The 9 cases of MMM with JAK2 mutations had only infrequent (2/9 cases) additional genomic alterations. Interestingly, No genomic alterations were noted in any of the cases (10) of ET having a normal Jak2. Two of 7 ET cases with JAK2 mutations had deletion of either 5q or trisomy 9. In summary, UPD is the predominant mechanism by which MPD develops homozygous JAK2 mutations. 1p UPD is a signpost that MPL is mutated in cases of MMM having wild-type JAK2; and these cells often have loss of Rb. ET cases with no JAK2 mutations are surprisingly free of genomic alterations.