Purpose: Though mutations of the calreticulin (CALR ) gene have been identified in essential thrombocythemia patients, the detailed mechanisms for CALR  mutations have not been completely clarified. Our study is aimed at characterizing alteration of protein expression in ET patients with mutated CALR^del52  and further recognizing possible involvement of signaling pathways associated with CALR  mutations.
Patients and Methods: Protein pathway array was performed to analyze the expression levels of proteins involved in various signaling pathways in peripheral blood neutrophils from 18 ET patients with mutated CALR^del52  , 20 ET patients with JAK2^V617F  mutation and 20 controls.
Results: We found 20 proteins differentially expressed in ET patients with mutated CALR^del52  compared with healthy controls. These proteins were associated with molecular mechanisms of cancer in ingenuity pathways analysis (IPA) network. We identified top ten canonical pathways which including apoptotic pathways and cellular cytokine pathways might participate in pathogenesis of ET with mutated CALR^del52 . Additionally, there were 8 proteins found to be dysregulated differently between ET patients with mutated CALR^del52  and those with JAK2^V617F  mutation. These proteins might be related to the unique signaling pathways activated by CALR^del52  mutation which were different to JAK/STATs pathway by JAK2^V617F  mutation.
Conclusion: Our study demonstrated that numerous alterations of signaling proteins and pathways in ET patients with mutated CALR^del52 . These findings could help to gain insights into the pathological mechanisms of ET.
Keywords: essential thrombocytosis, CALR^del52  mutation, protein pathway array, signaling proteins