scholarly journals The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal

2017 ◽  
Vol 177 (6) ◽  
pp. 1000-1007 ◽  
Author(s):  
Gyan K. Kayastha ◽  
Nora Ranjitkar ◽  
Radha Gurung ◽  
Raj Kumar KC ◽  
Sanjit Karki ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Mutation Analysis ◽  
Philadelphia Chromosome ◽  
Resistance Mutation ◽  
Imatinib Treatment ◽  
Imatinib Resistance

A Single Nucleotide Polymorphism in the Coding Sequence of BIM Is Associated with Poor Prognostic in Chronic Myeloid Leukaemia Treated by Imatinib

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1683-1683
Author(s):  
Francois-Xavier Mahon ◽  
Vanessa Augis ◽  
Kelly Airiau ◽  
Marina Josselin ◽  
Beatrice Turc ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Myeloid Leukaemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukaemia ◽  
Imatinib Treatment ◽  
Nucleotide Polymorphism ◽  
Deletion Polymorphism ◽  
Imatinib Resistance ◽  
Single Nucleotide ◽  
Coding Sequence

Abstract Abstract 1683 BIM is a pro-apoptotic protein essential to tyrosine kinase inhibitors (TKI) response in chronic myeloid leukaemia (CML) patients. Thus, mutations in BIM sequence could lead to imatinib resistance independently of BCR-ABL mutations. Recently, a deletion polymorphism in intron 2 of BIM was demonstrated to confer intrinsic TKI resistance in asiatic patients (Ng et al, nature medicine, 2012). However the Caucasian population is not concerned by this intronic deletion polymorphism. So, in the current study we performed BIM coding sequence analysis in 72 CML imatinib-treated patients and among them 40 were resistant to imatinib in our center from French population of patients. For twenty patients, the disease evolved in either acceleration or blastic phases at least once during the study. We did not find any mutation with amino-acid change in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710) in the region coding for the active BH3 domain. A strong statistic link was found between the presence of the T allele of this polymorphism and the Sokal high risk group (p=0.0065). The frequency of the T allele was found higher in non responsive patients than in a local healthy donor reference population (p=0.0049). Similarly, the analysis showed an association of this T allele with the frequency of mutations on the tyrosine kinase domain of BCR-ABL (p<0.001) but not with additional chromosomal alterations. Moreover, the presence of the allele T significantly lengthened the time of achievement of major molecular remission. Finally, the presence of the T allele was found related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy donors. These results suggest that analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of CML patients under imatinib treatment. Disclosures: Mahon: Novartis Pharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy.

scholarly journals Mutation Profiling of BCR-ABL Kinase Domain in Chronic Myeloid Leukaemia Patients with Imatinib Resistance

2020 ◽  
Author(s):  
Yuslina Mat Yusoff ◽  
Sharifah Zahra Anoar ◽  
Zahidah Abu Seman ◽  
Siti Shahrum Mohamed Said ◽  
Nor Rizan Kamaluddin ◽  
...  
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Mutational Analysis ◽  
Binding Capacity ◽  
Resistance Mutation ◽  
Treatment Decision ◽  
Kinase Domain ◽  
Imatinib Resistance ◽  
Abl Kinase ◽  
Patients At Risk

Abstract Objective: Emergence of mutation in the BCR-ABL kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contribute to IM resistance. Identification of these mutations is important for treatment decision and precision medicine in CML patients. Our study aims to determine the genomic landscape of BCR ABL KD mutations in CML patients with IM resistance. Result: BCR-ABL KD mutations were observed in 23 patients (26.7%). Fifteen different types of mutations have been identified; Y253H, E255K, T267A, K285I, A287T, M290R, F311I, T315I, F317L, F359V, F359I, F359C, K357T, A399T and E459K. We also discovered three novel mutations; M290R, K285I and K357T and two silent mutations at codon 389 and 401. Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance. Keywords: Chronic Myeloid Leukaemia; BCR-ABL kinase domain; imatinib resistance mutation.

scholarly journals Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Eric K. Newcott ◽  
Abdallah A. Ellabban ◽  
Shokufeh Tavassoli ◽  
Ahmed Sallam
Keyword(s):  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Macular Oedema ◽  
Intravitreal Bevacizumab ◽  
Imatinib Therapy ◽  
Cystoid Macular Oedema ◽  
Imatinib Treatment ◽  
Intravitreal Triamcinolone ◽  
Fellow Eye

Purpose.To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment.Methods.We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye.Results.Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision.Conclusion.Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia

2016 ◽  
Vol 69 (9) ◽  
pp. 810-816 ◽  
Author(s):  
Eda Tanrikulu Simsek ◽  
Ahmet Emre Eskazan ◽  
Mahir Cengiz ◽  
Muhlis Cem Ar ◽  
Seda Ekizoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Imatinib Therapy ◽  
Imatinib Treatment ◽  
Prognostic Impact ◽  
Bone Marrow Fibrosis ◽  
Significant Difference ◽  
Grade Ii ◽  
Marrow Fibrosis

AimsBefore the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy.MethodsThe study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated.ResultsSevere MF (grade II–III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0–I) and severe (grade II–III) groups (p=0.278).ConclusionsAccording to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.

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