scholarly journals Isolated ten-eleven translocation 2 positive in triple negative essential thrombocythemia: Case report and literature review

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110320
Author(s):  
Rehab Y AL-Ansari ◽  
Dena Al Otaibi ◽  
Nourah Al Hudaithi ◽  
Leena Abdalla
Keyword(s):  
Essential Thrombocythemia ◽  
Low Dose ◽  
Triple Negative ◽  
Clonal Evolution ◽  
Genetic Mutation ◽  
Deficiency Anemia ◽  
Thrombopoietin Receptor ◽  
Tet2 Mutation ◽  
High Platelet Count

Essential thrombocythemia is one of the famous diseases under the category of myeloproliferative disorder. It is an end result of a genetic mutation of one or more of the most frequent oncogenes such as Janos kinase 2 (JAK2), MPL proto-oncogene, thrombopoietin receptor (MPL), and calreticulin (CALR). However, negative genetic markers, so-called (triple negative disease), can happen in the presence of other uncommon types of mutation. TET2 (ten-eleven translocation 2) positive as isolated genetic marker in triple negative essential thrombocythemia is uncommon genetic presentation. For that, we are reporting a 22-year-old lady who presented with a feature of dyspepsia and accidentally found to have persistently high platelet count, even after treating her mild iron deficiency anemia with no other secondary causes. Further investigations and bone marrow biopsy supported the diagnosis of isolated TET2 positive in triple negative essential thrombocythemia. We treated her conservatively with good hydration and low dose of aspirin. In conclusion, isolated TET2 positive in triple negative essential thrombocythemia at presentation is uncommon with no clear management or risk stratification guideline. However, it is hypothesized that TET2 mutation precedes JAK2; therefore, the detection of isolated TET2 in a triple negative essential thrombocythemia case should be closely followed for clonal evolution in long term. Further study and guidelines required in this area.

scholarly journals Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients

Blood ◽  
2016 ◽  
Vol 127 (3) ◽  
pp. 333-342 ◽  
Author(s):  
Xénia Cabagnols ◽  
Fabrizia Favale ◽  
Florence Pasquier ◽  
Kahia Messaoudi ◽  
Jean Philippe Defour ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Triple Negative ◽  
Gain Of Function ◽  
Thrombopoietin Receptor ◽  
Key Points

Key Points Enrichment of atypical MPL mutations in essential thrombocythemia. MPLS204P and MPLY591N mutants are weak gain-of-function mutants.

scholarly journals Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy

2019 ◽  
Vol 9 (1) ◽  
pp. 64
Author(s):  
Clémence Dubois ◽  
Fanny Martin ◽  
Chervin Hassel ◽  
Florian Magnier ◽  
Pierre Daumar ◽  
...  
Keyword(s):  
Low Dose ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Breast Cancers ◽  
Treatment Protocols ◽  
Tnbc Cell ◽  
Cancer Subtype ◽  
Fractioned Irradiation ◽  
Activity Decrease

The Triple-Negative Breast Cancer subtype (TNBC) is particularly aggressive and heterogeneous. Thus, Poly-ADP-Ribose Polymerase inhibitors were developed to improve the prognosis of patients and treatment protocols are still being evaluated. In this context, we modelized the efficacy of Olaparib (i.e., 5 and 50 µM), combined with fractioned irradiation (i.e., 5 × 2 Gy) on two aggressive TNBC cell lines MDA-MB-231 (BRCAness) and SUM1315 (BRCA1-mutated). In 2D cell culture and for both models, the clonogenicity drop was 95-fold higher after 5 µM Olaparib and 10 Gy irradiation than Olaparib treatment alone and was only 2-fold higher after 50 µM and 10 Gy. Similar responses were obtained on TNBC tumor-like spheroid models after 10 days of co-treatment. Indeed, the ratio of metabolic activity decrease was of 1.2 for SUM1315 and 3.3 for MDA-MB-231 after 5 µM and 10 Gy and of only 0.9 (both models) after 50 µM and 10 Gy. MDA-MB-231, exhibiting a strong proliferation profile and an overexpression of AURKA, was more sensitive to the co-treatment than SUM1315 cell line, with a stem-cell like phenotype. These results suggest that, with the studied models, the potentiation of Olaparib treatment could be reached with low-dose and long-term exposure combined with fractioned irradiation.

scholarly journals Clinical characteristics of essential thrombocythemia patients depend on the mutation status

2020 ◽  
Vol 51 (4) ◽  
pp. 230-235
Author(s):  
Witold Prejzner ◽  
Andrzej Mital ◽  
Maria Bieniaszewska ◽  
Aleksandra Leszczyńska ◽  
Agata Szymańska ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Lower Risk ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Clinical Course ◽  
Janus Kinase ◽  
Overall Survival Rate ◽  
Mutation Status ◽  
Thrombopoietin Receptor ◽  
The Impact

AbstractThe impact of the mutation status on the clinical course and the outcome of essential thrombocythemia (ET) patients has not yet been completely established. A total of 171 patients with diagnosed ET were tested and subsequently grouped, according to their mutation status – Janus Kinase 2 (JAK2) – 112 patients, calreticulin (CALR) – 36 patients, and thrombopoietin receptor (MPL) – 5 patients. Moreover, 18 individuals were triple-negative (with non-mutated JAK2, CALR, and MPL). CALR-mutated patients preferentially were male, with higher platelets (PLT) counts (mean PLT = 1 002.3) and lower hemoglobin and hematocrit levels at the diagnosis, compared to the JAK2 (mean PLT = 933.6), MPL (mean PLT = 940.8) and triple-negative patients (mean PLT = 822.6) (p = 0.0035). The patients with CALR mutated, and the triple-negative ones had a lower risk of arterial and venous thrombosis (3% and 5.6% cases at the time of diagnosis, respectively) than the patients with JAK2 mutation (7.2%) (p = 0.9210). The overall survival rate did not differ statistically between the groups.

Ovarian Dysfunction in Fetally Irradiated Beagles

1977 ◽  
Vol 35 ◽  
pp. 658-659
Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Low Dose ◽  
Long Term Effects ◽  
Ovarian Dysfunction ◽  
Dose Rates ◽  
Highly Sensitive ◽  
Microscopic Evaluation ◽  
Ovarian Pathology ◽  
Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

Increased Thromboxane Biosynthesis in Essential Thrombocythemia

1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Essential Thrombocythemia ◽  
Therapeutic Strategy ◽  
Low Dose ◽  
Thrombotic Risk ◽  
Dose Aspirin ◽  
Gender And Age ◽  
Low Dose Aspirin

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

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