Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) 
have an inherent tendency to progress to acute myeloid leukemia (AML). Using 
high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients 
in different disease stages, including 77 AML cases with previous history of MPN 
(N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were 
detected, allowing the mapping of putative tumor suppressor genes involved in 
the leukemic transformation process. We detected frequent deletions on the short 
arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb 
region and contained only the JARID2 gene--member of the polycomb repressive 
complex 2 (PRC2). When we compared the frequency of del6p between chronic and 
leukemic phase, we observed a strong association of del6p with leukemic 
transformation (P = 0.0033). Subsequently, analysis of deletion profiles of 
other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and 
SUZ12; however, the deletions targeting these genes were large. We also 
identified two patients with homozygous losses of JARID2 and AEBP2. We observed 
frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next 
generation exome sequencing of 40 patients, we identified only one somatic 
mutation in the PRC2 complex member SUZ12. As the frequency of point mutations 
in PRC2 members was found to be low, deletions were the main type of lesions 
targeting PRC2 complex members. Our study suggests an essential role of the PRC2 
complex in the leukemic transformation of chronic myeloid disorders.