[The frequency of JAK2 V617F mutation, expression level of phosphorylated JAK/STATs proteins and their clinical significance in myeloproliferative disorders patients].
OBJECTIVE
To investigate the frequency of JAK2 V617F mutation in 145 myeloproliferative disorders (MPDs) patients, analyze the correlation between JAK2 V617F mutation and clinical features.


METHODS
The JAK2 V617F mutation was detected by direct DNA sequencing of PCR product and allele-specific PCR respectively. The expression of JAK2, phospho-JAK2 and phospho-STAT5 proteins was determined by Western blot. The clinical data of MPDs patients with or without JAK2 V617F mutation was collected and analyzed for evaluating the clinical significance of JAK2 V617F mutation.


RESULTS
1) The frequency of JAK2 V617F mutation for PV, IMF, ET was 92%, 58%, 50% respectively. Compared with conventional DNA sequencing (PV 84%, IMF 44%, ET 39%, respectively), allele-specific PCR exhibited a higher sensitivity in JAK2 V617F mutation detection. 2) The expression levels of phospho-JAK2 and phospho-STAT5 in peripheral blood mononuclear cells (PBMNCs) were upregulated significantly in JAK2 V617F-positive patients than in JAK2 V617F negative patients. 3) Compared with the patients with no JAK2 V617F mutation, the JAK2 V 617F-positive patients' features were as follows: older age of onset, higher mean leukocyte counts, lower platelet counts and smaller spleen volume. Frequency of thrombosis events in PT, ET, IMF was 17%, 32%, 16% respectively for JAK2 V617F positive group, and 0% (PV), 16% (ET), 5% (IMF) for JAK2 V617F negative group.


CONCLUSIONS
MPDs patients display higher frequency of JAK2 V617F mutation. JAK2 V617F mutation positive patients predispose to a thrombosis tendency.
Hu
Guo-Yu
GY
Department of Hematology, the Second Xiangya Hospital of Central South University, Changsha, China.
Deng
Ming-Yang
MY
Zhang
Guang-Sen
GS
Luo
Yun-Ya
YY
Zhu
Jian-Feng
JF
D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism; D017422:Sequence Analysis, DNA
D050799:STAT5 Transcription Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2