Sequential evaluation of CALR mutant burden in patients with myeloproliferative neoplasms
2017
// Chiara Cavalloni 1, * , Elisa Rumi 1, 2, * , Virginia V. Ferretti 2 , Daniela Pietra 2 , Elisa Roncoroni 2 , Marta Bellini 1 , Michele Ciboddo 1 , Ilaria C. Casetti 1 , Benedetta Landini 2 , Elena Fugazza 2 , Daniela Troletti 2 , Cesare Astori 2 , Mario Cazzola 1, 2 1 Department of Molecular Medicine, University of Pavia, Pavia, Italy 2 Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy * These authors contributed equally to this work Correspondence to: Elisa Rumi, email: elisarumi@hotmail.com , elisa.rumi@unipv.it Keywords: myeloproliferative, burden, CALR, JAK2, sequential Received: January 21, 2017 Accepted: March 24, 2017 Published: April 03, 2017 ABSTRACT We investigated the variation of CALR -mutant burden during follow-up in 105 CALR -mutant MPN and compared it to the variation of JAK2 -mutant burden in 226 JAK2 -mutant MPN. The median allele burden at last evaluation was significantly higher than at first evaluation in essential thrombocythemia (ET) (49.5% vs 45%, P < .001) but not in primary myelofibrosis (PMF) (52% vs 51%, P 0.398). Median values of slope were positive both in ET (0.071) and in PMF (0.032). In CALR -mutant ET there was a difference between natural and therapy-related slope ( P 0.006). In the JAK2 -mutated cohort, the median allele burden at last evaluation was not different respect to that at first evaluation, neither in ET (22.9% vs 23.2%, P = 0.216) nor in PMF (50.5% vs 45.0%, P = 0.809), despite a positive slope. Multivariate analysis to evaluate the effect of mutation ( CALR vs JAK2 ) on the slope of mutant burden in not treated pts with a positive slope adjusting for diagnosis (ET vs PMF) showed a trend toward a higher increase of mutant burden in CALR vs JAK2 (β = 0.19, P = 0.061) with no difference between diagnosis ( P = 0.419). The findings of this study suggest that clonal expansion in CALR-mutant MPN is faster than that observed in JAK2 -mutant MPN.
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