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Journal ArticleDOI

Evaluation of the association between the JAK2 46/1 haplotype and chronic myeloproliferative neoplasms in a Brazilian population

TL;DR: The JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in the studied population.
About: This article is published in Clinics.The article was published on 2013-01-01 and is currently open access. It has received 41 citations till now. The article focuses on the topics: Myeloproliferative neoplasm & Population.
Citations
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Journal ArticleDOI
TL;DR: Overall results showed that BDMC-A induced apoptosis more effectively compared to curcumin and the activity can be attributed to the presence of hydroxyl group in the ortho position in its structure.

50 citations

Journal ArticleDOI
TL;DR: These findings showed that JAK2V617F, as a diagnostic marker involving JAK 2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs.
Abstract: Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation. Discovery of CALR mutations led to the increased molecular diagnostic of ET and PMF up to 90%. It has been shown that JAK2V617F is not the unique event in disease pathogenesis. Some other genes' location such as TET oncogene family member 2 (TET2), additional sex combs-like 1 (ASXL1), casitas B-lineage lymphoma proto-oncogene (CBL), isocitrate dehydrogenase 1/2 (IDH1/IDH2), IKAROS family zinc finger 1 (IKZF1), DNA methyltransferase 3A (DNMT3A), suppressor of cytokine signaling (SOCS), enhancer of zeste homolog 2 (EZH2), tumor protein p53 (TP53), runt-related transcription factor 1 (RUNX1) and high mobility group AT-hook 2 (HMGA2) have also identified to be involved in MPNs phenotypes. Here, current molecular biology and genetic mechanisms involved in MNPs with a focus on the aforementioned factors is presented.

45 citations

Journal ArticleDOI
TL;DR: In this article, a review of the potential biological and social mechanisms through which fathers might exert an impact on the health of their offspring is presented, and a systematic compiled overview of the current evidence linking paternal factors to offspring development of obesity and type 2 diabetes throughout the life course is presented.
Abstract: The aetiologies of obesity and type 2 diabetes are incredibly complex, but the potential role of paternal influences remains relatively understudied. A better understanding of paternal influences on offspring risk of obesity and type 2 diabetes could have profound implications for public health, clinical practice and society. In this review, we outline potential biological and social mechanisms through which fathers might exert an impact on the health of their offspring. We also present a systematically compiled overview of the current evidence linking paternal factors to offspring development of obesity and type 2 diabetes throughout the life course. Although evidence is accumulating to support paternal associations with offspring outcomes, more high-quality research is needed to overcome specific methodological challenges and provide stronger causal evidence.

36 citations

Journal ArticleDOI
TL;DR: The presence of the JAK2 V617F mutation is considered the most important criterion in the diagnosis of breakpoint cluster region-Abelson fusion oncogene-negative neoplasms and is thus used as a clonal marker.
Abstract: Myeloproliferative neoplasms are caused by a clonal proliferation of a hematopoietic progenitor. First described in 1951 as 'Myeloproliferative Diseases' and reevaluated by the World Health Organization classification system in 2011, myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia and primary myelofibrosis in a subgroup called breakpoint cluster region-Abelson fusion oncogene-negative neoplasms. According to World Health Organization regarding diagnosis criteria for myeloproliferative neoplasms, the presence of the JAK2 V617F mutation is considered the most important criterion in the diagnosis of breakpoint cluster region-Abelson fusion oncogene-negative neoplasms and is thus used as a clonal marker. The V617F mutation in the Janus kinase 2 (JAK2) gene produces an altered protein that constitutively activates the Janus kinase/signal transducers and activators of transcription pathway and other pathways downstream as a result of signal transducers and activators of transcription which are subsequently phosphorylated. This affects the expression of genes involved in the regulation of apoptosis and regulatory proteins and modifies the proliferation rate of hematopoietic stem cells.

30 citations

Journal ArticleDOI
TL;DR: It is found that, in Drosophila melanogaster, components of reproductive success in females, but not males, were contingent on the nature of sexual interactions experienced by their mothers, highlighting the importance of non-sire influences ofSexual interactions on the expression of offspring life histories.
Abstract: The consequences of sexual interactions extend beyond the simple production of offspring. These interactions typically entail direct effects on female fitness, but may also impact the life historie...

29 citations

References
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Book
29 Sep 2017
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Abstract: WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

13,835 citations

Journal ArticleDOI
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Abstract: background Polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are clonal myeloproliferative disorders arising from a multipotent progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases. methods We performed microsatellite mapping of the 9pLOH region and DNA sequencing in 244 patients with myeloproliferative disorders (128 with polycythemia vera, 93 with essential thrombocythemia, and 23 with idiopathic myelofibrosis). results Microsatellite mapping identified a 9pLOH region that included the Janus kinase 2 ( JAK2 )

3,391 citations


"Evaluation of the association betwe..." refers background or methods or result in this paper

  • ...Blood samples were also collected from 90 healthy individuals (blood donors from the Hemocentro Regional de Maringá) and used as controls, as the JAK2 V617F mutation is not found in healthy individuals (3-6,13,14)....

    [...]

  • ...The JAK2 V617F mutation was identified in more than 95% of PV patients and in approximately half of the patients with ET and MF but was not observed in healthy individuals (2-6)....

    [...]

  • ...As shown in Table 1, the characteristics of the studied patients are very similar to those observed in the literature (2-5), which indicates the comparability of our data and supports the assertion that the presence of the G allele is a pivotal factor in the development of cMPN in our population....

    [...]

  • ...It was observed that the JAK2 V617F mutation could occur in a homozygous or heterozygous fashion in the affected hematopoietic cells (2-5)....

    [...]

Journal ArticleDOI
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.

3,326 citations


"Evaluation of the association betwe..." refers background or methods or result in this paper

  • ...Blood samples were also collected from 90 healthy individuals (blood donors from the Hemocentro Regional de Maringá) and used as controls, as the JAK2 V617F mutation is not found in healthy individuals (3-6,13,14)....

    [...]

  • ...The JAK2 V617F mutation was identified in more than 95% of PV patients and in approximately half of the patients with ET and MF but was not observed in healthy individuals (2-6)....

    [...]

  • ...As shown in Table 1, the characteristics of the studied patients are very similar to those observed in the literature (2-5), which indicates the comparability of our data and supports the assertion that the presence of the G allele is a pivotal factor in the development of cMPN in our population....

    [...]

  • ...It was observed that the JAK2 V617F mutation could occur in a homozygous or heterozygous fashion in the affected hematopoietic cells (2-5)....

    [...]

Journal ArticleDOI
28 Apr 2005-Nature
TL;DR: A clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (> 80%) polycythaemia vera patients leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model.
Abstract: Myeloproliferative disorders are clonal haematopoietic stem cell malignancies characterized by independency or hypersensitivity of haematopoietic progenitors to numerous cytokines(1,2). The molecular basis of most myeloproliferative disorders is unknown. On the basis of the model of chronic myeloid leukaemia, it is expected that a constitutive tyrosine kinase activity could be at the origin of these diseases. Polycythaemia vera is an acquired myeloproliferative disorder, characterized by the presence of polycythaemia diversely associated with thrombocytosis, leukocytosis and splenomegaly(3). Polycythaemia vera progenitors are hypersensitive to erythropoietin and other cytokines(4,5). Here, we describe a clonal and recurrent mutation in the JH2 pseudo-kinase domain of the Janus kinase 2 (JAK2) gene in most (>80%) polycythaemia vera patients. The mutation, a valine-to-phenylalanine substitution at amino acid position 617, leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity and induces erythrocytosis in a mouse model. As this mutation is also found in other myeloproliferative disorders, this unique mutation will permit a new molecular classification of these disorders and novel therapeutical approaches.

3,326 citations


"Evaluation of the association betwe..." refers background or methods or result in this paper

  • ...Blood samples were also collected from 90 healthy individuals (blood donors from the Hemocentro Regional de Maringá) and used as controls, as the JAK2 V617F mutation is not found in healthy individuals (3-6,13,14)....

    [...]

  • ...The JAK2 V617F mutation was identified in more than 95% of PV patients and in approximately half of the patients with ET and MF but was not observed in healthy individuals (2-6)....

    [...]

  • ...As shown in Table 1, the characteristics of the studied patients are very similar to those observed in the literature (2-5), which indicates the comparability of our data and supports the assertion that the presence of the G allele is a pivotal factor in the development of cMPN in our population....

    [...]

  • ...It was observed that the JAK2 V617F mutation could occur in a homozygous or heterozygous fashion in the affected hematopoietic cells (2-5)....

    [...]

Journal ArticleDOI
15 Sep 2005-Blood
TL;DR: It is concluded that V617F is widespread in MPDs and detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy.

843 citations


"Evaluation of the association betwe..." refers background or result in this paper

  • ...The JAK2 V617F mutation was identified in more than 95% of PV patients and in approximately half of the patients with ET and MF but was not observed in healthy individuals (2-6)....

    [...]

  • ...As shown in Table 1, the characteristics of the studied patients are very similar to those observed in the literature (2-5), which indicates the comparability of our data and supports the assertion that the presence of the G allele is a pivotal factor in the development of cMPN in our population....

    [...]

  • ...Homozygosity frequently occurs for a specific allele through duplication of the mutated allele and consequent loss of the non-mutated allele (2)....

    [...]

  • ...It was observed that the JAK2 V617F mutation could occur in a homozygous or heterozygous fashion in the affected hematopoietic cells (2-5)....

    [...]