scholarly journals TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Dratwa ◽  
Barbara Wysoczańska ◽  
Aleksandra Butrym ◽  
Piotr Łacina ◽  
Grzegorz Mazur ◽  
...  

AbstractAcute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.

2019 ◽  
Vol 102 (3) ◽  
pp. 218-226
Author(s):  
Marie Warny ◽  
Jens Helby ◽  
Henrik Sengeløv ◽  
Børge G. Nordestgaard ◽  
Henrik Birgens ◽  
...  

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4898-4898
Author(s):  
Nabila Chellakhi ◽  
Nissrine Khoubila ◽  
Siham Cherkaoui ◽  
Abdallah Madani ◽  
Uma Athale ◽  
...  

Abstract Introduction: The outcome of acute myeloid leukaemia (AML) in emerging countries is very dismal. In Morocco,the complete remission rate (CR) has improved from less of 10% in 1980s to more than 60% in 2000s. However this improvement is far from satisfactory to improve five year survival rate. The aim of study was to evaluate preliminary outcomes of children ≤15years treated according to AML- MA 11protocol. Methods : Between the first January 2011 to December 2014, we carrieed a prospective study of all children aged 15 years or less, diagnosed AML. The diagnosis was according by cytological study with cytochemestry: MPO positive (FAB classification), supplemented by immunophenotyping. The prognosis is evaluated by conventional cytogenetic study. AML-MA 2011 protocol consisted of prephase(whenwhite blood cell (WBC) count ≥ 50 G/l) by Hydroxyurea (HU) (50 mg/m2/day for 4 days). The response to HU was evaluated after 2 days; patients were considered responsers if >50% reduction of the initial WBC count. Then 2 inductions based on daunorubicin 50 mg/m2 (3 days), cytarabine 100mg/m2/12 hours (10 days) and etoposide 100 mg/m2 (5 days) for the second course, followed by 3 consolidations with high dose of cytarabine 1-3 g/m2/12 hours (3 days), with intrathecal therapy. The supportive care is assured during all phases of treatment. Results: Forty four patients were enrolled with a median age of 8 years [1-15] and M:F ratio of 1.2. The median WBC count was 22710 elements/mm3; it exceeded 50 000/mm3 in 18 % of cases, more than 100 000/mm3 in 13 % of cases.The cytological studies showed the predominance of AML subtype 2 (31%) followed by subtype 5 (11, 3%). The immunophenotyping was done in 88% of cases. Karyotype performed in 40 out of 44 cases revealed: 9 (22,5%) favorable risk group [8 had the t(8,21); 1 had inv16], 25 (62,5%) intermediate risk, and 6 (15%) unfavorable-risk group. Seven patients received hydroxy urea with 5 good response (71% of cases; 2 patients had favorable risk and 3 had intermediate risk). Four of this patients died. Thirty five patients were treated (3 death before treatment, 4 abandonment of treatment, 1 myelodysplasea syndroma, and 1 bad condition). After the induction cycles; complete remission was achieved in 22 cases (62%), failure in 6 cases, and 7 children dead (20%) [4 septic choc, 2 haemorrhage and 1 acute pulmonary edema]. One patient died between 0 to 14 days during the cure and 6 others after 14 days of treatment. After a mean follow-up of 9months (1 to 43 months), continuous complete remission was achieved in 45,7% of cases, failure in 20%, relapse in 11%, and death in 45,45 % of cases. (toxic death in 25% of cases with high frequence in induction phases: 88%). Theoverall survival rate in 2 years was 41,2%. Table. Evolution of patients according to prognostic groups Status/cytogenetic groups CR (%) Failure (%) Death (%) Relapse (%) OS (%) favorable 55 0 11 22 53,3 intermediate 32 32 16 4 34,4 unfavorable 33 16 16 16 55,6 Conclusion: With aggressive chemotherapy, it is feasible to achieve high CR even in emerging countries. If supportive care is optimal with particular focus on prevention and management of infection and with improved transfusion support, then it's feasible to improve the overall outcome of patients. Finally it is necessary to make the molecular biology in our patients topreciselyindividualize the pronostic groups. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Naeem Jabbar ◽  
Neelum Mansoor ◽  
Sidra Maqsood ◽  
Zaid Muhammad Aslam ◽  
Anzal Taufeeq Jangda ◽  
...  

Abstract Objective: To find the frequency of core binding factor acute myeloid leukaemia in our population, and to determine its association with morphological subtypes. Methods: The retrospective study was conducted at The Indus Hospital, Karachi, and comprised data of patients aged 1-17 years who were diagnosed with acute myeloid leukaemia from July 2013 to June 2017. Data was analysed using SPSS 21. Results: Of the 237 patients, 137(58%) were males and 100(42%) were females. The overall mean age was 8±4.34 years. Cytogenetic testing had been performed in 212(89.45%) cases, and core binding factor was detected in 72(34%) cases. There was significant difference between the mean values of white cell count and the subtypes (p=0.000). Also the difference between core binding factor and the subtypes was significant (p=0.000). Conclusion: There was found to be a significant association of core binging factor with specific subgroups of acute myeloid leukaemia. Key Words: Acute myeloid leukaemia, Core binding factor, Cytogenetic abnormalities, Prognosis. Continuous....


2019 ◽  
Vol 19 (4) ◽  
pp. 233-234
Author(s):  
Jorrit Schaefer ◽  
Sorcha Cassidy ◽  
Rachel M. Webster

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