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|Title:||Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms||Authors:||Thoennissen, N.H.
Phillip Koeffler, H.
|Issue Date:||8-Apr-2010||Citation:||Thoennissen, N.H., Krug, U.O., Lee, D.H.T., Kawamata, N., Iwanski, G.B., Lasho, T., Weiss, T., Nowak, D., Koren-Michowitz, M., Kato, M., Sanada, M., Shih, L.-Y., Nagler, A., Raynaud, S.D., Müller-Tidow, C., Mesa, R., Haferlach, T., Gilliland, D.G., Tefferi, A., Ogawa, S., Phillip Koeffler, H. (2010-04-08). Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood 115 (14) : 2882-2890. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2009-07-235119||Abstract:||Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions.We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F- cases with MPN-blast phase. Remarkably, copy number-neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia. © 2010 by The American Society of Hematology.||Source Title:||Blood||URI:||http://scholarbank.nus.edu.sg/handle/10635/126840||ISSN:||00064971||DOI:||10.1182/blood-2009-07-235119|
|Appears in Collections:||Staff Publications|
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