Oncotarget

Research Papers:

Sequential evaluation of CALR mutant burden in patients with myeloproliferative neoplasms

Chiara Cavalloni, Elisa Rumi _, Virginia V. Ferretti, Daniela Pietra, Elisa Roncoroni, Marta Bellini, Michele Ciboddo, Ilaria C. Casetti, Benedetta Landini, Elena Fugazza, Daniela Troletti, Cesare Astori and Mario Cazzola

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Oncotarget. 2017; 8:33416-33421. https://doi.org/10.18632/oncotarget.16797

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Abstract

Chiara Cavalloni1,*, Elisa Rumi1,2,*, Virginia V. Ferretti2, Daniela Pietra2, Elisa Roncoroni2, Marta Bellini1, Michele Ciboddo1, Ilaria C. Casetti1, Benedetta Landini2, Elena Fugazza2, Daniela Troletti2, Cesare Astori2, Mario Cazzola1,2

1Department of Molecular Medicine, University of Pavia, Pavia, Italy

2Department 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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