Development of a highly sensitive method for detection of JAK2V617F

Zhao, Anna H.; Gao, Runping; Zhao, Zhizhuang Joe

doi:10.1186/1756-8722-4-40

Cited by 16 publications

(18 citation statements)

References 37 publications

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“…The presence of JAK2V617F was readily detected by using a simple allele-specific PCR technique [13] (data not shown). We further amplified a DNA fragment covering the exon 14 of JAK2 by PCR with genomic DNA as templates.…”

Section: Resultsmentioning

confidence: 99%

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

Zhao

et al. 2012

Exp Hematol Oncol

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BackgroundJAK2V617F, 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.MethodsTotal 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.ResultsHomozygous 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.ConclusionsJAK2V617F 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.

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Section: Resultsmentioning

confidence: 99%

“…DNA sequencings were performed from both forward and reserve directions. To determine the ratio of JAK2 and JAK2V617F at the genomic or cDNA level, real time PCR analyses were performed as previously described [14], except that purified plasmid DNAs were used as standards [13]. …”

Section: Methodsmentioning

confidence: 99%

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

Zhao

et al. 2012

Exp Hematol Oncol

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“…The specific and profound involvement of JAK-STAT pathway in various hematological malignancies, especially Bcr-Abl negative MPNs, makes them ideal targets for pharmacological intervention [57]. Several strategies have been proposed to inhibit or modulate this pathway [58,59].…”

Section: Novel Inhibitors Of Jak-stat Pathwaymentioning

confidence: 99%

Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application

Furqan

Mukhi

Lee³

et al. 2013

Biomark Res

154

123

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JAK-STAT (Janus associated kinase-signal transducer and activator of transcription) pathway plays a critical role in transduction of extracellular signals from cytokines and growth factors involved in hematopoiesis, immune regulation, fertility, lactation, growth and embryogenesis. JAK family contains four cytoplasmic tyrosine kinases, JAK1-3 and Tyk2. Seven STAT proteins have been identified in human cells, STAT1-6, including STAT5a and STAT5b. Negative regulators of JAK–STAT pathways include tyrosine phosphatases (SHP1 and 2, CD45), protein inhibitors of activated STATs (PIAS), suppressors of cytokine signaling (SOCS) proteins, and cytokine-inducible SH2-containing protein (CIS). Dysregulation of JAK-STAT pathway have been found to be key events in a variety of hematological malignancies. JAK inhibitors are among the first successful agents reaching clinical application. Ruxolitinib (Jakafi), a non-selective inhibitor of JAK1 & 2, has been approved by FDA for patients with intermediate to high risk primary or secondary myelofibrosis. This review will also summarize early data on selective JAK inhibitors, including SAR302503 (TG101348), lestaurtinib (CEP701), CYT387, SB1518 (pacritinib), LY2784544, XL019, BMS-911543, NS-018, and AZD1480.

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“…Cell pellets were preserved for future use at -20°C. DNA was extracted, and JAK2 mutation V617F was detected at diagnosis with nested allele-specific polymerase chain reaction (PCR) as described previously [11]. Samples with low DNA content were pre-amplified and 1.0 µL of product was amplified by nested PCR.…”

Section: Analysis Of Jak2 Mutation V617f and Exon 12mentioning

confidence: 99%

Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2-mutated polycythemia vera

Bai

Zhang

et al. 2015

Am. J. Hematol.

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Development of a highly sensitive method for detection of JAK2V617F

Cited by 16 publications

References 37 publications

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

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

Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application

Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2-mutated polycythemia vera

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