scholarly journals HOXA4Gene Promoter Hypermethylation as an Epigenetic Mechanism Mediating Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Marjanu Hikmah Elias ◽  
Abdul Aziz Baba ◽  
Azlan Husin ◽  
Sarina Sulong ◽  
Rosline Hassan ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Clinical Problem ◽  
Promoter Hypermethylation ◽  
Epigenetic Silencing ◽  
Epigenetic Mechanism ◽  
High Resolution Melt ◽  
High Resolution Melt Analysis ◽  
Development Of Resistance

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation ofHOXA4could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status ofHOXA4in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, theHOXA4hypermethylation level was significantly higher (P=0.002) in IM-resistant CML patients. On comparing the risk,HOXA4hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673–12.971;P=0.003). Thus, it is reasonable to suggest that promoter hypermethylation ofHOXA4gene could be an epigenetic mechanism mediating IM resistance in CML patients.

scholarly journals Bcr-Abl Expression Levels Determine the Rate of Development of Resistance to Imatinib Mesylate in Chronic Myeloid Leukemia

2005 ◽  
Vol 65 (19) ◽  
pp. 8912-8919 ◽  
Author(s):  
David J. Barnes ◽  
Danai Palaiologou ◽  
Eleni Panousopoulou ◽  
Beate Schultheis ◽  
Agnes S.M. Yong ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Rate Of Development ◽  
Expression Levels ◽  
Development Of Resistance

Effects of imatinib mesylate on normal bone marrow cells from chronic myeloid leukemia patients in complete cytogenetic response

2009 ◽  
Vol 33 (1) ◽  
pp. 170-173 ◽  
Author(s):  
Fermin M. Sanchez-Guijo ◽  
Jesus M. Hernandez ◽  
Eva Lumbreras ◽  
Patricia Morais ◽  
Carlos Santamaría ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Cytogenetic Response ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Complete Cytogenetic Response ◽  
Marrow Cells

scholarly journals Safety Profile of Imatinib in Indian Chronic Myeloid Leukemia Patients

1970 ◽  
Vol 9 (1) ◽  
pp. 24-30
Author(s):  
R Meena ◽  
NR Biswas ◽  
Lalit Kumar ◽  
T Velpandian ◽  
YK Gupta
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Imatinib Mesylate ◽  
Safety Profile ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Specific Inhibitor ◽  
Chronic Phase ◽  
Symptomatic Treatment ◽  
Weight Changes

Introduction: Imatinib mesylate has become the choice of drug in the treatment of chronic myeloid leukemia. Objective: To study safety profile of Imatinib (specific inhibitor or bcrabl tryosne kinase protein) in Philadelphia chromosome t {(9:22), bcr-abl} positive chronic myeloid leukemia (CML) chronic phase patients. Materials and Methods: After IEC clearance, 36, BCR-ABL positive CML patients in the chronic phase of the disease were recruited. Imatinib mesylate (Gleevec, Novartis), was started (400mg daily) and followed up weekly in first month, two weekly till three months & monthly thereafter. Safety profile data, recorded in pre-designed proforma, were analyzed for time of onset, duration and severity of adverse effects. Causality relationship of recorded adverse events was established with imatinib therapy using WHO-UMC criteria. Results: A total of 222 adverse events were reported in 36 CML-CP patients over 12 months of follow up. Thrombocytopenia was the most commonly reported in 60% of the patients followed by musculoskeletal (17%), dermatological (16%), gastrointestinal disturbances (13%), body weight changes (11%), superficial edema (8%) and liver enzyme rise (4%). More than 80% events reported within months of therapy which persisted for less than 3 months in most of the cases. No treatment was needed in 68% of cases while therapy alteration was not needed in 88% of cases. Most of the reactions (60%) had probable relationship with the therapy. Conclusion: Imatinib was well tolerated, having only mild to moderate grade of toxicities, mostly within 3 months of therapy and most of them persisted for less than 3 months of duration, requiring only symptomatic treatment and drug withhold or dose decrement in only few cases. Keywords: Safety profile; imatinib; causality assessment; adverse events. DOI: 10.3126/hren.v9i1.4358Health Renaissance, 2011: Vol.9 No.1:24-30

scholarly journals Positive response to imatinib mesylate therapy for childhood chronic myeloid leukemia

2010 ◽  
Vol 43 (6) ◽  
pp. 580-584
Author(s):  
G.A.P. Oliveira ◽  
E.S. Costa ◽  
M.S. Freitas ◽  
F.F. Dutra ◽  
S.F. Maia ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Positive Response

scholarly journals Imatinib mesylate-induced generalized hypopigmentation in patients with chronic myeloid leukemia

2006 ◽  
Vol 38 (1) ◽  
pp. 66 ◽  
Author(s):  
Sunita ◽  
M Sharma ◽  
DK Gupta ◽  
S Saluja ◽  
S Bhasin
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia
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