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Since 2005, the discovery of the somatic mutation V617F in exon 14 of the Janus Kinase 2 gene (JAK2) was the front-line molecular tool for the diagnosis of  Myelproliferative neoplasms (MPN) of which essential thrombocythemia (ET). In addition, detection of genetic alteration in the 10th exon of the myeloproliferative leukemia gene (MPL) plays a significant role in the pathogenesis of ET. However, about 40% of patients did not carry any of these markers and the diagnosis of ET remained a major challenge. Towards the end of 2013, somatic mutations in the 9th exon of the gene encoding calreticulin (CALR) were revealed to be responsible of MPN in around 80% of ET patients who don’t carry the JAK2 or MPL mutations. 

This discovery have improved and simplified the accuracy of diagnosis of patients with ET worldwide, and opened the door to a better understanding of the disease pathogenesis. In this study, we present the 1st mutational profiles in CALR gene assessed in Moroccan Patients.

25 Moroccan patients from Clinical Hematology Department of the Military Hospital Mohammed V were reviewed for having ET. All patients had a CBC with elevated platelet count; We searched magakaryocytes proliferation at the bone marrow biopsy for only 8 patients. The bcr-abl transcript was negative for all patients. The mutational status for exon 10 of MPL gene has not been evaluated in any of our patients. We evaluate somatic mutation V617F in JAK2 gene and mutations in 9th exon of CALR.

Patients ages were between 23 and 75 years, 13 of them were female. Discovery circumstances ranged from fortuitous discovery to thrombotic or hemorrhagic manifestations. Median platelet countat diagnosis was 1 027 578 /mm3. Molecular assessment of the somatic mutation V617F in JAK2 gene was positive in eight, negative in 13 patients, 4 patients were not evaluated. Among the 13 “JAK2 negative” patients mutations in 9th exon of CALR were evaluated in 11 patients and were detected in four of them (36.3%). All the variants found were insertion/deletion mutations; All mutations were found between positions 1142 and 1157 in the coding DNA sequence (cDNA). Patients with intermediate and high risk received therapy such as hydroxyurea (13 patients), anagrelide (2 patients), pipobroman (4 patients) to lower the platelet count.

CALR gene mutations discovery represented a major milestone in the diagnosis of ET that would be highly considered in the revision of the WHO classification of MPN. Up to date, comparative studies on the treatment of CALR mutated patients with ET were not yet reported and further studies should help to explore this area.