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The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms

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Abstract

Somatic mutations in the CALR gene were recently discovered in a substantial proportion of Philadelphia-negative chronic myeloproliferative neoplasm (cMPN) patients lacking JAK2 and MPL mutations. Somatically acquired defects are not the only pathogenic mechanism involved in these disorders. Since germline JAK2 46/1 haplotype predisposes to cMPN-associated mutations, including JAK2V617F and MPLW515K7L, we evaluated whether the 46/1 haplotype also confers susceptibility to CALR-mutated cMPN, both in sporadic and familial cases. The single-nucleotide polymorphism rs10974944, which tags 46/1, was investigated in 155 sporadic MPN patients and 270 unrelated controls, as well as in 11 familial cMPN cases and 36 unaffected relative controls. As described elsewhere, the 46/1 haplotype was overrepresented, both in sporadic and familial cMPN. In sporadic cMPN, the JAK2 46/1 haplotype was closely associated with JAK2V617F (p = 0.0003) but not with JAK2-nonmutated cases. Analysis of CALR-mutated sporadic cMPN (n = 22) showed no association between CALR mutations and 46/1 haplotype (p = 0.87). Regarding the familial cMPN, the prevalence of carriers of the G allele was higher in familial (81.8 %) than in sporadic (62 %) cMPN, but it did not differ significantly (p = 0.3). Although we described a family with carriers of both JAK2V617F and CALR mutations, due to the low number of CALR-mutated familial cases, we could not determinate whether the JAK2 46/1 haplotype predisposes or does not to CALR-mutated familial cMPN. We conclude, for the first time, that the 46/1 haplotype, unlike JAK2V617F and MPLW515K7L, is not associated with CALR-mutated cMPN.

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Acknowledgments

We thank N Navarro for her technical assistance and J Corral for the critical review of the manuscript.

Conflict of interest

The authors report no conflict of interests in this article.

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Authors and Affiliations

  1. Hematology and Medical Oncology Unit, Hospital Universitario Morales-Meseguer, Centro Regional de Hemodonacion, IMIB-Arrixaca, C/Ronda de Garay, sn. 3003, Murcia, Spain

    G. Soler, A. Bernal-Vicente, A. I. Antón, J. M. Torregrosa, E. Caparrós-Pérez, B. Sánchez-Vega, V. Vicente & F. Ferrer-Marin

  2. Hematology Unit, Northwest Hospital, Caravaca, Murcia, Spain

    I. Sánchez-Serrano

  3. Unit of Genomics of Complex Diseases, Institute of Biomedical Research (II-B Sant Pau), Barcelona, Spain

    A. Martínez-Pérez

  4. Laboratory of Molecular Genetics, Gemolab S.L., Madrid, Spain

    B. Sánchez-Vega

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  1. G. Soler
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  2. A. Bernal-Vicente
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  3. A. I. Antón
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  4. J. M. Torregrosa
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  5. E. Caparrós-Pérez
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  6. I. Sánchez-Serrano
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  7. A. Martínez-Pérez
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  8. B. Sánchez-Vega
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  9. V. Vicente
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  10. F. Ferrer-Marin
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Correspondence to F. Ferrer-Marin.

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Soler, G., Bernal-Vicente, A., Antón, A.I. et al. The JAK2 46/1 haplotype does not predispose to CALR-mutated myeloproliferative neoplasms. Ann Hematol 94, 789–794 (2015). https://doi.org/10.1007/s00277-014-2266-y

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  • DOI: https://doi.org/10.1007/s00277-014-2266-y

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