Prevalence and Prognostic Impact of Allelic Imbalances Associated with Leukemic Transformation of Philadelphia Chromosome-negative Myeloproliferative Neoplasms

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2010 Jan 14

PMID 20068225

Citations 56

Authors

Nils H Thoennissen

Utz O Krug

Dhong Hyun Tony Lee

Norihiko Kawamata

Gabriela B Iwanski

Terra Lasho

Tamara Weiss

Daniel Nowak

Maya Koren-Michowitz

Motohiro Kato

Masashi Sanada

Lee-Yung Shih

Arnon Nagler

Sophie D Raynaud

Carsten Muller-Tidow

Ruben Mesa

Torsten Haferlach

D Gary Gilliland

Ayalew Tefferi

Seishi Ogawa

H Phillip Koeffler

Affiliations

Soon will be listed here.

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.

Citing Articles

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