Conflict of interest: Nothing to report.
Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies†
Article first published online: 21 DEC 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Hematology
Volume 87, Issue 3, pages 245–250, March 2012
How to Cite
Puda, A., Milosevic, J. D., Berg, T., Klampfl, T., Harutyunyan, A. S., Gisslinger, B., Rumi, E., Pietra, D., Malcovati, L., Elena, C., Doubek, M., Steurer, M., Tosic, N., Pavlovic, S., Guglielmelli, P., Pieri, L., Vannucchi, A. M., Gisslinger, H., Cazzola, M. and Kralovics, R. (2012), Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. Am. J. Hematol., 87: 245–250. doi: 10.1002/ajh.22257
- Issue published online: 13 FEB 2012
- Article first published online: 21 DEC 2011
- Accepted manuscript online: 18 NOV 2011 08:04AM EST
- Manuscript Received: 15 NOV 2011
- Manuscript Accepted: 15 NOV 2011
- Austrian Science Fund. Grant Number: P23257-B12
- MPN Research Foundation, Fondazione Cariplo, Regione Lombardia
- MPO. Grant Number: FR-TI2/254
- Associazione Italiana per la Ricerca sul Cancro (AIRC, Milano) “Special Program Molecular Clinical Oncology 5x1000” to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative - ; studies in Pavia and Florence) [http://www-progettoagimm.it]. Grant Numbers: #1005, IG 9034
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. Am. J. Hematol. 2012. © 2011 Wiley Periodicals, Inc.