Calreticulin mutations are not present in patients with myeloproliferative chronic myelomonocytic leukemia

Dear Editor, Chronic myelomonocytic leukemia (CMML) has been classified into a new category of myelodysplastic/myeloproliferative diseases (MDS/MPN) according to the last WHO classification of myeloid malignancies [1]. However, some patients with CMML show proliferative features (MP-CMML) such as leukocytosis and organomegaly, making them clinically and biologically similar to myeloproliferative neoplasms (MPN). At biological level, JAK2V617F mutations in MP-CMML have been described at a lower frequency than in MPN [2]. Recently, CALR gene mutations have been described in 67–88 % JAK2V617F and MPL-negative MPN; these cases also have a good prognosis [3–7]. The role of CALR mutations in CMML is not well known, and the few studies carried out so far have not focused on MP subtype [3, 4, 8]. The objective of this study was to characterize the frequency, type, and prognostic implications of CALR mutations in MP-CMML. CALR exon 9 mutations were studied in 30 patients (22 males, median age 66 years) diagnosed of CMML according toWHO classification [1], and all of them belonged to MP-CMML according to the French-American-British Co-operative Leukaemia Group (Table 1). All patients provided informed consent for sample collection. Biological analyses were carried out in accordance with the Declaration of Helsinki. Mutation analysis was performed as previously described [3]. An informative result was obtained in 29/30 patients, and no CALR exon 9 mutation was found. Although a small percentage of mutated MP-CMML patients was expected [4], no mutations were detected in the samples studied. These results are in concordance with those of Klampfl T et al. [3] and Hou et al. [8], who found no CALR mutations in 64 and 48 CMML patients, respectively (subtype not specified), but they do differ from the results of Nangalia et al., who found 1/33 CMML mutated patient (subtype not specified) [4]. There is also another study [9] of other MDS/ MPN groups (atypical CML and unclassifiable MDS/MPN) where CALR mutations were not seen in either entity (n=30). Therefore, outside essential thrombocythemia and primary myelofibrosis, CALR mutations are only found in (1) a few patients with MDS/MPN, most of them defined as having refractory anemia with ring sideroblasts associated with marked thrombocytosis, even though the percentage described is very variable depending on the series (0 to 12.5 %) [3, 4, 10] and (2) a few MDS patients, mainly with refractory anemia with ring sideroblasts, refractory anemia, and refractory anemia with excess blasts [3, 4, 8, 10]. This observation could indicate a relationship between CALR mutations and the thrombocytosis phenotype within myeloid neoplasms, suggesting that calreticulin mutations primarily affect the biology of megakaryocytes [11]. L. Zamora (*) :M. Cabezon : S. Marce : L. Palomo : F. Milla : E. Feliu : B. Xicoy ICO Badalona, Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucemia Josep Carreras, Badalona, Spain e-mail: lzamora@iconcologia.net