Publication Date:
2007-11-16
Description:
Recently, the identification of the gain of function mutation JAK2V617F delivered important insights into the pathogenesis of BCR/ABL negative myeloproliferative disorders (MPD). JAK2V617F is detectable in more than 90% of polycythemia vera (PV) patients (pts) and in approximately 50% of pts with essential thrombocythemia (ET) or primary myelofibrosis (PMF), representing the genetic hallmark of BCR/ABL negative disease. However, about 30% of MPD pts lack the JAK2V617F mutation and previous studies on ET and PV demonstrated that clonality exceeds the percentage of V617F mutated cells. These findings suggest that additional genetic alterations are involved in the pathogenesis of MPD, in both JAK2 mutated and unmutated pts. To identify novel genetic aberrations and to determine whether specific lesions are associated with disease phenotype, genomic DNA from granulocytes of 72 MPD pts classified according to the WHO criteria was analyzed using high-resolution, genome-wide microarray techniques [disease, number analyzed, JAK2 mutation status: PMF, n=14, 9/14; post-ET MF, n=5, 3/5; post-PV MF, n=5, 5/5; PV, n=37, 37/37; ET, n=11, 11/11]. In a first approach, all cases were investigated by comparative genomic hybridization to 8k arrays (array CGH) with an average probe spacing of less than 1 Mb. While no genomic imbalances were found in ET, 11% of PV pts (n=4) exhibited large (〉10 Mb) deletions on 20q (n=2) or gains on 9p and 1q (n=1, each). In addition, small (
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
