title: SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.
abstract: We applied single nucleotide polymorphism arrays (SNP-A) to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD), including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2 V617F mutation and secondary acute myeloid leukemia (AML). In typical MPD cases (N = 8), which served as a control group, those with a homozygous V617F mutation showed clear uniparental disomy (UPD) of 9p using SNP-A. Consistent with possible genomic instability, in 19/30 MDS/MPD-U patients, we found additional lesions not identified by metaphase cytogenetics. In addition to UPD9p, we also have detected UPD affecting other chromosomes, including 1 (2/30), 11 (4/30), 12 (1/30) and 22 (1/30). Transformation to AML was observed in 8/30 patients. In 5 V617F+ patients who progressed to AML, we show that SNP-A can allow for the detection of two modes of transformation: leukemic blasts evolving from either a wild-type jak2 precursor carrying other acquired chromosomal defects, or from a V617F+ mutant progenitor characterized by UPD9p. SNP-A-based detection of cryptic lesions in MDS/MPD-U may help explain the clinical heterogeneity of this disorder.
authors.affiliation: Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Lukasz P
authors.initials: LP
authors.lastname: Gondek
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dunbar
authors.forename: Hadrian
authors.initials: H
authors.lastname: Szpurka
authors.forename: Michael A
authors.initials: MA
authors.lastname: McDevitt
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
mesh_terms: D001483:Base Sequence; D002869:Chromosome Aberrations; D017931:DNA Primers; D006801:Humans; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy
chemical_list: D017931:DNA Primers