• Christopher Allen, Jonathan R Lambert, David C Linch, and Rosemary E Gale.
• Department of Haematology, University College London Cancer Institute, London, United Kingdom.
• Blood. 2014 Sep 25; 124 (13): 2091-3.

AbstractCalreticulin mutations (CALR(MUT)) are found in a significant proportion of patients with essential thrombocythemia (ET) lacking JAK2(V617F) or MPL mutations. They are associated with substantially different hematological and clinical features and define a distinct subtype of ET. We show here that their presence is significantly correlated with a clonal X chromosome inactivation pattern (XCIP). Of 105 female ET patients investigated, 61 had an interpretable XCIP, and a clonal pattern was observed in 88% of CALR(MUT) patients compared with 26% of JAK2(V617F) (P = .0002) and 9% of JAK2(V617F)/MPL/CALR wild-type patients (P < .0001). Neutrophil CALR(MUT) level was significantly higher than JAK2(V617F) level (median, 50% vs 18%; P < .0001), and wild-type myelopoiesis was suppressed in CALR(MUT) but not JAK2(V617F) patients. These data are suggestive of truly monoclonal hematopoiesis in CALR(MUT) patients and provide further evidence that the biology associated with CALR mutations is markedly different from that of JAK2(V617F) mutations. © 2014 by The American Society of Hematology.

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