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JAK2V617F and p53 mutations coexist in erythroleukemia and megakaryoblastic leukemic cell lines

Wanke Zhao1, Yanhong Du1, Wanting Tina Ho1, Xueqi Fu2 and Zhizhuang Joe Zhao12*

Author Affiliations

1 Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

2 Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun, China

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Experimental Hematology & Oncology 2012, 1:15  doi:10.1186/2162-3619-1-15

Published: 21 June 2012



JAK2V617F, a gain-of-function mutant form of tyrosine kinase JAK2, is found in the majority of patients with Ph- myeloproliferative neoplasms (MPNs), a group of chronic hematological diseases that often lead to acute leukemia. The current study is intended to find other gene mutations that collaborate with JAK2V617F to cause leukemic transformation.


Total RNA and genomic DNA were isolated from two JAK2V617F-positive cell lines, namely, erythroleukemic HEL and megakaryoblastic leukemic SET-2 cells. Candidate genes were amplified by PCR and further sequenced.


Homozygous mutations of the TP53 gene which encodes tumor suppressor p53 were found in HEL and SET-2 cells. While HEL cells, which have homozygous JAK2V617F, contain a rare M133K p53 mutation, SET-2 cells, which have a heterozygous JAK2V617F mutation, contain a common R248W p53 alteration. Western blot analyses revealed high levels of p53 expression in both cells. M133K and R248W are located in the DNA binding domain of p53. Structural analyses revealed that they potentially disrupt the interaction of p53 with DNA, thereby causing loss of p53 function.


JAK2V617F and p53 mutations coexist in leukemia cells. We believe that JAK2V617F is able to drive leukemic transformation when the function of tumor suppressor p53 is lost. The interplay of JAK2V617F with p53 may affect the progression of MPNs.

JAK2; TP53; Leukemia; Mutations; Transformation