Guideline on myeloproliferative neoplasms: Associacão Brasileira de Hematologia, Hemoterapia e Terapia Cellular

Tavares, Renato; Nonino, Alexandre; Pagnano, Kátia Bórgia Barbosa; Nascimento, Ana Clara Kneese Virgilio do; Conchon, Mônika; Fogliatto, Laura; Funke, Vaneuza Araújo Moreira; Bendit, Israel; Clementino, Nelma Cristina D.; Chauffaille, Maria de Lourdes Lopes Ferrari; Bernardo, Wanderley Marques; Santos, Fábio Pires de Souza

doi:10.1016/j.htct.2019.03.001

Cited by 4 publications

(7 citation statements)

References 297 publications

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“…A high haemoglobin level was more prominent in JAK2 positive patients compared to others according to the literature 7,14,18 . Our findings were compatible with the literature regarding the haemoglobin level.…”

Section: Discussionsupporting

confidence: 92%

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JAK2V617F , CALR and MPL515L/K mutations and plateletcrit in essential thrombocythemia: A single centre's experience

et al. 2020

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Aims JAK2V617F (JAK2), calreticulin (CALR) and MPL515L/K (MPL) mutations are important in essential thrombocythemia (ET) and may be associated with various clinical consequences of the disease. This study aimed to compare the clinical and haematological parameters of ET patients regarding the mentioned mutations and the role of plateletcrit (PCT). Methods Seventy patients who were diagnosed with ET between 2005 and 2017 in a single centre were included in this descriptive study. The initial symptoms and clinical findings were retrieved from the electronic database. JAK2 gene V617F mutations, MPL gene exon 10 mutations and CALR gene exon 9 DNA sequence analyses were performed. Forty‐one healthy volunteers were included to perform ROC curve analysis for interpreting PCT value. Results The distributions of patients according to the mutations were as follows: Thirty‐seven (52.9%) patients were JAK2‐positive, 15 (21.4%) were CALR‐positive, 2 (2.8%) patients were positive for both CALR and JAK2, and 1 (1.4%) was only MPL‐positive. Fifteen (21.4%) patients were triple‐negative. The ET patients with JAK2 mutation showed a higher level of haemoglobin at the time of diagnosis. The ET patients with CALR mutation presented with higher platelet and LDH levels (P = .002 and P = .001, respectively). The PCT level was higher in the CALR‐positive group when compared to the others (P = .026). A sensitivity value of 97.6% and specificity value of 98.6% were determined regarding PCT% at a cut‐off value of 0.37 in ET patients. In CALR‐positive patients, the sensitivity and specificity values were 100% for the PCT at a cut‐off value of 0.42%. Conclusion We determined that the platelet count and blood LDH level was high in the ET patient group with CALR mutation. Besides, we found that the blood haemoglobin level was higher in the ET patient group with JAK2 mutation. Additionally, the PCT level was higher in the CALR group when compared to the other patient groups.

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Section: Discussionsupporting

confidence: 92%

“…A high haemoglobin level was more prominent in JAK2 positive patients compared to others according to the literature. 7,14,18 Our findings were compatible with the literature regarding the haemoglobin level. We found a statistically lower level of LDH in the TN group compared to the CALR-positive patients.…”

Section: Discussionsupporting

confidence: 92%

JAK2V617F , CALR and MPL515L/K mutations and plateletcrit in essential thrombocythemia: A single centre's experience

et al. 2020

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“…JAK2 is a tyrosine kinase activated by cytokines receptors, which triggers pathways such as PI3K/AKT, MAPK, and others, increasing cell proliferation and reducing apoptosis (Hu et al, 2021). Nowadays, MPN treatment is still mainly for control constitution symptoms and complications (Tavares et al, 2019). Ruxolitinib, a JAK2 inhibitor, is approved for intermediate or high-risk PMF patients and those PV patients with inadequate response or intolerance to hydroxyurea, leading to an improvement of constitutional symptoms and splenomegaly but not inducing a complete molecular response or bone marrow fibrosis reduction in MF (Tavares et al, 2019;Tefferi, 2021).…”

Section: Focal Adhesion Kinase Inhibition Decreases Cell Viability An...mentioning

confidence: 99%

“…Nowadays, MPN treatment is still mainly for control constitution symptoms and complications (Tavares et al, 2019). Ruxolitinib, a JAK2 inhibitor, is approved for intermediate or high-risk PMF patients and those PV patients with inadequate response or intolerance to hydroxyurea, leading to an improvement of constitutional symptoms and splenomegaly but not inducing a complete molecular response or bone marrow fibrosis reduction in MF (Tavares et al, 2019;Tefferi, 2021). Furthermore, many patients present intolerance or develop resistance to ruxolitinib, mainly by loss of response.…”

Section: Focal Adhesion Kinase Inhibition Decreases Cell Viability An...mentioning

confidence: 99%

Focal adhesion kinase inhibition decreases cell viability and induces apoptosis of JAK2 V617F positive cells

Valente,

Farias,

Bernardo

et al. 2023

Braz. J. Pharm. Sci.

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Focal Adhesion Kinase (FAK) protein participates in proliferation, migration, cell survival, and apoptosis process. It has been described as overexpressed in several neoplasms being a promising target for therapy. BCR-ABL negative chronic Myeloproliferative Neoplasms (MPN) are clonal disorders characterized by the excess of proliferation and apoptosis resistance. The identification of the acquired JAK2 V617F mutation in MPN patients allowed a better understanding of pathogenesis. However, there is still no pharmacological treatment that leads all patients to molecular remission, justifying new studies. The present study aimed to evaluate FAK involvement in the viability and apoptosis of HEL and SET-2 cells, both JAK2 V617F positive cell lines. The FAK inhibitor PF 562,271 was used. Cell viability was determined using MTT assay and apoptosis verified by cleaved PARP, cleaved Caspase 3 and Annexin-V/PI staining detection. FAK inhibition significantly reduced HEL and SET-2 cells viability and induced apoptosis. Considering the role of JAK/STAT pathway in MPN, further investigation of FAK participation in the MPN cells proliferation and apoptosis resistance, as well as possible crosstalk between JAK and FAK and downstream pathways may contribute to the knowledge of MPN pathophysiology, the discovery of new molecular targets, and JAK inhibitors resistance mechanisms.

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“…Furthermore, the older sister had a trisomy 8 (47, XX, +8) karyotype and 40% JAK2 V617F mutation in the bone marrow, and her outcome was more severe than that of the younger sister, who had a normal karyotype and 100% JAK2 V617F mutation in the bone marrow. Research has shown that patients with trisomy 8 mosaicism are at a higher risk of developing leukemia (29), and karyotype abnormalities are associated with lower survival in the univariate analysis (30). A higher mutation frequency of JAK2 V617F in PMF is associated with an unfavorable cytogenetic profile, and the presence of unfavorable cytogenetic abnormalities is significantly associated with decreased survival (31).…”

Section: Summary Of the Two Casesmentioning

confidence: 99%

Somatically acquired mutations in primary myelofibrosis: A case report and meta‑analysis

et al. 2021

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Guideline on myeloproliferative neoplasms: Associacão Brasileira de Hematologia, Hemoterapia e Terapia Cellular

Cited by 4 publications

References 297 publications

JAK2V617F , CALR and MPL515L/K mutations and plateletcrit in essential thrombocythemia: A single centre's experience

JAK2V617F , CALR and MPL515L/K mutations and plateletcrit in essential thrombocythemia: A single centre's experience

Focal adhesion kinase inhibition decreases cell viability and induces apoptosis of JAK2 V617F positive cells

Somatically acquired mutations in primary myelofibrosis: A case report and meta‑analysis

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