In:
Journal of Clinical Laboratory Analysis, Wiley, Vol. 30, No. 6 ( 2016-11), p. 1061-1070
Kurzfassung:
Despite recent advances in the investigation of myeloproliferative neoplasms ( MPN ), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera ( PV ) and essential thrombocythemia ( ET ). Methods We conducted association studies using 84 single‐nucleotide polymorphisms ( SNP s) in 229 patients (96 with PV and 133 with ET ) and 170 controls. Further, whole‐genome sequencing was performed in six patients (two with JAK 2 V617F and four with wild‐type JAK 2 ), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. Results Several germline SNP s and the 46 haplotype were significantly associated with PV and ET . Three somatic mutations in MPDZ , IQCH , and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK 2 / MPL mutations. Moreover, compared with JAK 2 V617F‐positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels ( P = 0.004 and P = 0.002, respectively), higher platelet counts ( P =0.008), and a lower frequency of cytoreductive therapy ( P = 0.014). Conclusion This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET . We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.
Materialart:
Online-Ressource
ISSN:
0887-8013
,
1098-2825
DOI:
10.1002/jcla.2016.30.issue-6
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2016
ZDB Id:
2001635-9