RAPID COMMUNICATION High frequency of MEFV gene mutations in patients with myeloid neoplasm Cagatay Oktenli • Ozkan Sayan • Serkan Celik • Alev A. Erikci • Yusuf Tunca • Hakan M. Terekeci • Elcin Erkuvan Umur • Yavuz S. Sanisoglu • Deniz Torun • Fatih Tangi • Burak Sahan • Selim Nalbant Received: 26 February 2010 / Revised: 7 April 2010 / Accepted: 14 April 2010 / Published online: 1 May 2010 Ó The Japanese Society of Hematology 2010 Abstract We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neo- plasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with mye- loid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promo- tion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies. Keywords MEFV mutation Á Myeloid neoplasms Á Acute myeloid leukemia Á Chronic myeloid leukemia Á Myelodysplastic syndrome Á Polycythemia vera 1 Introduction Familial Mediterranean fever (FMF) is an autoinflammatory disease of unknown etiology primarily found in populations originating from the Mediterranean basin, mostly Turks, Druze, Levantine Arabs, Armenians and Sephardic Jews [1– 3]. The gene responsible for FMF, symbolized ‘‘MEFV’’, located on chromosome 16p.13.3, was identified by posi- tional cloning by two independent consortia in 1997 [4, 5]. To date, over 150 FMF-associated mutations have been described [6]. However, five of those mutations (M694V, M680I, V726A, E148Q and M694I) are responsible for about 80% of the FMF cases and they are all located in exon 10, except for E148Q mutations [7]. The MEFV gene is predominantly expressed in myeloid cells, and its expression is upregulated during myeloid differentiation [8, 9]. This gene is responsible for encoding a protein called pyrin (or marenostrin) [4, 5, 10]. The pyrin domain can bind indirectly to at least two proteins important in inflammation: pro-cas- pase-1 and the inhibitor of nuclear factor-jB (NF-jB) kinase complex [11–13]. Thus, the production of IL-1b is inhibited and normal apoptosis is allowed. On the other hand, pyrin may be able to modify the NF-jB pathway and apoptosis independently of IL-1b [14–17]. C. Oktenli (&) Á S. Celik Á H. M. Terekeci Á E. E. Umur Á F. Tangi Á B. Sahan Á S. Nalbant Division of Internal Medicine, GATA Haydarpasa Training Hospital, 34668 Kadikoy, Istanbul, Turkey e-mail: coktenli@yahoo.com; coktenli@ttmail.com O. Sayan Á A. A. Erikci Division of Hematology, GATA Haydarpasa Training Hospital, Istanbul, Turkey Y. Tunca Á D. Torun Department of Medical Genetics, Gu ¨lhane Military Medical Academy, Ankara, Turkey Y. S. Sanisoglu Department of Monitoring and Evaluation, Turkish Ministry of Health, Ankara, Turkey 123 Int J Hematol (2010) 91:758–761 DOI 10.1007/s12185-010-0577-x