scholarly journals MicroRNA-150 down Regulation in Acute Myeloid Leukaemia Patients and Its Prognostic Implication

2018 ◽  
Vol 6 (11) ◽  
pp. 1993-2000 ◽  
Author(s):  
Dalia Adel Abdelhalim ◽  
Basma M. Elgamal ◽  
Mona R. ElKafoury ◽  
Naglaa M. Hassan ◽  
Marwa M. Hussein ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Target Genes ◽  
De Novo ◽  
Response To Treatment ◽  
Variable Response ◽  
Significant Difference ◽  
The Impact ◽  
Acute Myeloid

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that are important for post-transcriptional gene regulation in both healthy and morbid conditions. Numerous miRNAs promote tumorigenesis, while others have a tumour suppressive effects. Acute myeloid leukaemia (AML) is a heterogeneous group of genetically diverse hematopoietic malignancies with variable response to treatment. AIM: Our study aimed to investigate the possible role of miR-150 in de novo adult AML and the impact of its level on survival, and we used in the silicon analysis to predict the main target genes involved in miR-150 mediated cancer pathway. MATERIAL AND METHODS: We evaluated miR-150 expression profiling assay using TaqMan primer probes RT-PCR in the plasma of 50 adult AML patients, before the start of treatment and at day 28 of treatment, along with 20 normal adult control samples. miR-16 was used as an endogenous reference for standardisation. Follow-up of patients during treatment at day 28 of induction chemotherapy and after one year was done. RESULTS: In this study, we found a significantly lower level of miR-150 in AML patients when compared to controls (p = 0.005) with 0.62 fold change than in healthy controls. Patients were divided into two groups: the low miR-150 group (miR-150 < 1) and the high miR-150 group (miR-150 > 1). A statistically significant difference was found between the two groups regarding initial total leukocytic count and initial PB blast count while for the TLC, HB and PLT count at follow up. No difference in the overall survival between the low and the high miR-150 groups could be demonstrated. CONCLUSION: Our results suggest that miR-150 functions as a tumour suppressor and gatekeeper in inhibiting cell transformation and that its downregulation is required for leukemogenesis.

Increased Use of Allogeneic Transplant in CR2 Improves the Outcome for Children with Acute Myeloid Leukaemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2521-2521
Author(s):  
Aditi Vedi ◽  
Richard Mitchell ◽  
Cecelia Oswald ◽  
Glenn M Marshall ◽  
Toby Trahair ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Supportive Care ◽  
Myeloid Leukaemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Induction Treatment ◽  
Allogeneic Transplant ◽  
Significant Difference ◽  
Related Mortality ◽  
Acute Myeloid

Abstract Improvements in Outcome for Paediatric de novo Acute Myeloid Leukaemia Aditi Vedi1,2, Richard Mitchell1, Cecelia Oswald1, Glenn Marshall1,2, Toby Trahair1, David S Ziegler1,2 1Kids Cancer Centre, Sydney ChildrenÕs Hospital, Randwick, NSW, Australia, 2 School of Women and Children's Health, University of New South Wales, Randwick, NSW, Australia ABSTRACT The treatment for paediatric acute myeloid leukaemia (AML) has not changed significantly over the past 3 decades, yet outcomes have improved with cure rates increasing from 30% to over 50% of all newly diagnosed children over this period. This improvement in survival has been attributed to both treatment intensification and improved supportive care over the decades, although the precise impact of each remains unknown. Our group has retrospectively analysed a unique cohort of patients with de novo AML diagnosed in childhood (n=276), all treated with the same chemotherapy protocol over a 25-year period from 1986-2012. The contemporary cohort (2000-12), compared to historical cohorts (1986-99) had significantly improved overall survival (OS, 75% vs. 50%, p = 0.01), lower disease related mortality (38% vs. 19%, p = 0.02) and were significantly more likely to receive allogeneic transplant after relapse (SCT, 73% vs. 12%, p <0.0001). Allogeneic transplant post relapse was associated with a significantly improved survival across the entire cohort (OS 50% for allogeneic SCT vs. 12% for autologous or none, p<0.0001). There was no significant difference between the contemporary and historical cohorts in treatment related mortality (13% vs. 7%, p = 0.42) or relapse rates after induction (50% in older cohort vs. 40% in recent era, p=0.25), suggesting consistency of induction treatment efficacy and toxicity across the two periods. This data suggests improved survival in paediatric AML in the modern era has predominantly resulted from increased use of allogeneic SCT after relapse rather than from improved supportive care and is independent of chemotherapy intensification. Disclosures No relevant conflicts of interest to declare.

scholarly journals Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

2016 ◽  
Vol 50 (4) ◽  
pp. 385-393 ◽  
Author(s):  
Marijana Virijevic ◽  
Teodora Karan-Djurasevic ◽  
Irena Marjanovic ◽  
Natasa Tosic ◽  
Mirjana Mitrovic ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
De Novo ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Isocitrate Dehydrogenase 1 ◽  
The Stability ◽  
Acute Myeloid

Abstract Background Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection.

The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy for AML Improves Disease Free Survival without Extra Toxicity: Preliminary Analysis of 1115 Patients in the MRC AML15 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 13-13 ◽  
Author(s):  
Alan K. Burnett ◽  
William J. Kell ◽  
Anthony H. Goldstone ◽  
Donald Milligan ◽  
Ann Hunter ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preliminary Analysis ◽  
De Novo ◽  
Remission Rate ◽  
Pilot Trial ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Significant Difference ◽  
The Impact

Abstract The MRC AML15 Trial is primarily for patients with any form of AML who are under 60 years. One of the questions addressed was whether the addition of the immunoconjugate, Gemtuzumab Ozogamicin (GO) to induction (course 1) and/or consolidation (course 3) is beneficial. In induction patients are randomised to receive either DA (Daunorubicin/Ara-C) or ADE (Ara-C/Daunorubicin/Etoposide) or FLAG-Ida (Fludarabine/Ara-C/Idarubicin/G-CSF) and in consolidation either MACE (Amsacrine/Etoposide) or HD Ara-C (3.0g/m2 or 1.5g/m2 per dose). Our prior pilot trial had shown that GO 3mgs/m2 could be safely added to day 1 of each of these treatments (Kell et al Blood102, 4277–4283). Here we report the preliminary results of the effect of combining GO with induction chemotherapy. This randomisation achieved its recruitment target and was closed on 30 June 2006. All other comparisons in the trial, including GO in consolidation, remain open. Patients: A total of 1115 patients were randomised between July 2002 and June 2006. The median age was 49 (range 0–71) years: 53% of patients were male: 92% (n=1027) had de novo disease: 95% had WHO performance score of &lt;2: 43% received DA, 43% FLAG-Ida, and 14% ADE. (Recruitment to ADE+GO opened in June 2005). Patients with WBC &gt; 30 x 109/l and LFT’s &gt; normal were initially excluded but admitted from March 2004. APL patients were not eligible for entry. 15% of patients with data had favourable 71% intermediate, and 14% adverse cytogenetics. Over 83% were CD33 positive. Results: The overall remission rate was 85% with no differences between the arms for GO vs no GO in CR (85% vs 85%) induction death (8% vs 7%) or resistant disease (7% vs 8%). There was a modest increase in mucositis on the GO arm in course 1 only (p=0.04) and increased AST and Alt toxicity in C1 (p=.002; p=.03) but no difference in bilirubin grades. GO patients used more platelets (19 vs 14; p&lt;0.0001), but not red cells, and had more days on IV antibiotics (20.6 vs 18.6 p=0.001). The haemopoietic recovery and days in hospital were similar. With a median follow-up of 15 months (range 0–45), there is no significant difference in deaths in CR (GO vs no GO): 36 vs 45 (HR 0.75; CI.49–1.16 p=0.2), but relapse was reduced: 37% vs 52% at 3 years (HR 0.70 (0.52–0.92) p=0.01) resulting in an improved DFS: 51% vs 40% at 3 years (HR 0.72 (0.56–0.91) p=0.008). There is so far no significant difference in OS (53% vs 46% at 3 years; HR 0.91(0.73–1.14) p=0.4). Conclusion: This preliminary analysis of 1115 randomised patients indicates that the addition of GO to induction chemotherapy can reduce the relapse risk without adding significant extra toxicity and this has significantly improved the DFS in the GO arm. Longer follow up is required to determine the impact on survival.

High risk of ‘de novo’ acute myeloid leukaemia in individuals with cytochrome P450 A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) gene defects

2009 ◽  
Vol 83 (3) ◽  
pp. 270-272 ◽  
Author(s):  
Gabriela Góes Yamaguti ◽  
Gustavo Jacob Lourenço ◽  
Fernando Ferreira Costa ◽  
Carmen Silvia Passos Lima
Keyword(s):  
Cytochrome P450 ◽  
High Risk ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
De Novo ◽  
Gene Defects ◽  
Acute Myeloid
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