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Korean J Lab Med. 2010 Dec;30(6):567-574. Korean.
Published online December 02, 2010.  https://doi.org/10.3343/kjlm.2010.30.6.567
Copyright © 2010 The Korean Society for Laboratory Medicine
JAK2 V617F and Exon 12 Genetic Variations in Korean Patients with BCR/ABL1-negative Myeloproliferative Neoplasms
Jeong Tae Kim, M.D.,1 Yong Gon Cho, M.D.,1 Sam Im Choi, M.D.,1 Young Jin Lee, M.D.,2 Hye Ran Kim, Ph.D.,3 Sook Jin Jang, M.D.,4,5 Dae Soo Moon, M.D.,4 Young Jin Park, M.D.,4 and Geon Park, M.D.4,5
1Department of Laboratory Medicine, Chonbuk National University Medical School, Jeonju, Korea.
2Department of Laboratory Medicine, Wonkwang University Medical School, Iksan, Korea.
3Brain Korea 21 Project, Center for Biomedical Human Resource at Chonnam National University, Gwangju, Korea.
4Department of Laboratory Medicine, Chosun University Medical School, Gwangju, Korea.
5Research Center for Resistant Cells, Chosun University Medical School, Gwangju, Korea.

Corresponding author: Geon Park, M.D. Department of Laboratory Medicine, Chosun University Medical School, 588 Seoseok-dong, Dong-gu, Gwangju 501-717, Korea. Tel: +82-62-220-3272, Fax: +82-62-232-2063, Email: creatgeon@chosun.ac.kr
Received April 30, 2010; Revised September 30, 2010; Accepted October 14, 2010.

Abstract

Background

JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). This study was designed to analyze the frequencies of JAK2 V617F and exon 12 variations, and their correlations with clinical characteristics of Korean patients with BCR/ABL1-negative MPN.

Methods

We examined a total of 154 patients with BCR/ABL1-negative MPN that included 24, 26, 89, and 15 patients with polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and unclassified myeloproliferative neoplasms (MPNU), respectively. We performed allele-specific PCR to detect V617F in all BCR/ABL1-negative patients, and performed direct sequencing to detect exon 12 variations in 47 V617F-negative MPN patients. JAK2 c.1641+179_183del5 variation was detected by restriction fragment length polymorphism assay in 176 healthy subjects.

Results

JAK2 V617F was detected in 91 patients (59.1%): PV (91.6%), PMF (46.2%), ET (52.8%), and MPNU (66.7%). In V617F-negative MPN patients, no mutations were found in exon 12. The c.1641+179_183del5 was detected in 68.1% of V617F-negative MPN patients and 45.4% of healthy subjects (P=0.008). JAK2 V617F was closely correlated with age and leukocytosis in BCR/ABL1-negative MPN patients (P<0.05). However, c.1641+179_183del5 was not related to age, sex, or complete blood cell count parameters in V617F-negative MPN patients and healthy subjects. The c.1641+179_183del5 was associated with an increased odds ratio for MPN (odds ratio, 2.6; 95% confidences interval, 1.3-5.1; P=0.007).

Conclusions

Frequencies of V617F are similar to reported results. JAK2 exon 12 mutations may be rare and c.1641+179_183del5 may influence the occurrence of MPN in Korean patients with V6 17F-negative MPN.

Keywords: Myeoloproliferative neoplasms; JAK2; V617F; Exon 12; rs56241661

Figures


 Fig. 1
The allele-specific PCR assay for detecting JAK2 V617F mutation in patients with BCR/ABL1-negative myeloproliferative neoplasms. The 364 bp of PCR product is an internal control and 203 bp is a mutant specific product. Lane SM, φX174/HindIII DNA size marker (TaKaRa, Siga, Japan); lane 1, JAK2 V617F mutation positive control; lane 2, JAK2 V617 wild negative control; lanes 3 and 6, positive results from clinical samples; lanes 4 and 5, negative results from clinical samples; lane D/W, deionized water.
Click for larger image


Fig. 2
The restriction fragment length polymorphism assay for detecting JAK2 c.1641+179_183del5 genetic variation in normal subjects. Lane SM, φX174/HindIII DNA size marker (TaKaRa, Siga, Japan); lane 1, homozygotic wild control; lane 2, heterozygotic variant control; lane 3, homozygotic variant control; lane 4, homozygotic wild type; lane 5, heterozygotic variant type.
Click for larger image

Tables


 Table 1
Clinical laboratory characteristics of the patients with BCR/ABL1-negative myeloproliferative disorders at the time of bone marrow examination and comparison of the clinical laboratory characteristics according to the mutational status of JAK2 V617F
Click for larger image


Table 2
Clinical characteristics of patients with JAK2 V617F-negative myeloproliferative neoplasms and normal subjects according to the JAK2 c.1641+179_183del5 (rs56241661) genetic variation
Click for larger image

Notes

The present study was supported by grants from the Chosun University (2008).

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