Allelic expression imbalance of JAK2 V617F mutation in BCR-ABL negative myeloproliferative neoplasms.
The discovery of a single point mutation in the JAK2 gene in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs) has not only brought new insights and pathogenesis, but also has made the diagnosis of MPNs much easier. Although, to date, several mechanisms for the contribution of single JAK2V617F point mutation to phenotypic diversity of MPNs have been suggested in multiple studies, but it is not clear how a unique mutation can cause the phenotypic diversity of MPNs. In this study, our results show that allelic expression imbalance of JAK2 V617F mutant frequently occurs and contributes to phenotypic diversity of BCR-ABL-negative MPNs. The proportion of JAK2 V617F mutant allele was significantly augmented in RNA levels as compared with genomic DNA differently by distinct MPNs subtypes. In detail, preferential expression of JAK2 mutant allele showed threefold increase from the cDNA compared with the genomic DNA from patients with essential thrombocythemia and twofold increase in polycythemia vera. In conclusion, allelic expression imbalance of JAK2 V617F mutant proposes another plausible mechanism for the contribution of single JAK2 point mutation to phenotypic diversity of MPNs.
Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University, Gwangju, South Korea.
Hye-Ran
HR
Kim
Hyun-Jung
HJ
Choi
Yeo-Kyeoung
YK
Kim
Hyeoung-Joon
HJ
Kim
Jong-Hee
JH
Shin
Soon-Pal
SP
Suh
Dong-Wook
DW
Ryang
Myung-Geun
MG
Shin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D017354:Point Mutation; D016896:Treatment Outcome; D055815:Young Adult
D005819:Genetic Markers; D016044:Fusion Proteins, bcr-abl; D053614:Janus Kinase 2