The prognostic impact of germline 46/1 haplotype of Janus Kinase 2 in cytogenetically normal acute myeloid leukemia

Sarolta Nahajevszky, Hajnalka Andrikovics, Arpad Batai, Emma Adam, Andras Bors, Judit Csomor, Laszlo Gopcsa, Magdalena Koszarska, Andras Kozma, Nora Lovas, Sandor Lueff, Zoltan Matrai, Nora Meggyesi, Janos Sinko, Andrea Sipos, Andrea Varkonyi, Sandor Fekete, Attila Tordai, Tamas Masszil

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Abstract

Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype.

Original languageEnglish
Pages (from-to)1613-1618
Number of pages6
JournalHaematologica
Volume96
Issue number11
DOIs
Publication statusPublished - Nov 1 2011

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Keywords

  • 46/1 haplotype
  • Acute myeloid leukemia
  • Janus Kinase 2
  • Prognosis

ASJC Scopus subject areas

  • Hematology

Cite this

Nahajevszky, S., Andrikovics, H., Batai, A., Adam, E., Bors, A., Csomor, J., Gopcsa, L., Koszarska, M., Kozma, A., Lovas, N., Lueff, S., Matrai, Z., Meggyesi, N., Sinko, J., Sipos, A., Varkonyi, A., Fekete, S., Tordai, A., & Masszil, T. (2011). The prognostic impact of germline 46/1 haplotype of Janus Kinase 2 in cytogenetically normal acute myeloid leukemia. Haematologica, 96(11), 1613-1618. https://doi.org/10.3324/haematol.2011.043885