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H396R, F359V and E255K mutations of the Abl kinase domain in imatinib-resistant Nigerian patients with chronic myeloid leukemia

Anthony Adebukola Oyekunle, Rahman Bolarinwa, Temilola Owojuyigbe, Oche Ogbe, Lateef Salawu, Julius Faluyi, Muheez Durosinmi


AIM We have observed therapy failure in some Nigerian patients with chronic myeloid leukemia (CML). We therefore set out to determine the causes of imatinib resistance in these patients.

METHODS From August 2003 to July 2010, we registered and commenced 266 consenting CML patients on imatinib (IM) under the Glivec International Patient Assistance Program (GIPAP). We investigated the occurrence of Abl kinase domain mutations (KDM) among a cohort of these patients, with features of imatinib resistance or intolerance. Peripheral blood samples were collected from 14 patients, after informed consent was obtained for Bcr-Abl quantitative PCR assessment and Abl KDM screening.  

RESULTS The chimeric Bcr-Abl gene was detectable in all patients, (range of 0.18 - 141.9%), when compared with the Abl gene. Sequencing analysis was done in 12 out of the 14 patients and Abl KDM were identified in three of the 12 patients (one quarter). One mutant (H396R) is known to retain intermediate sensitivity to imatinib, while the other two (E255K and F359V) are insensitive; all are sensitive to nilotinib. Four of these patients have since been commenced on nilotinib and are responding well to therapy, while three have died of disease progression.

CONCLUSION An increasing number of Nigerian CML patients on imatinib are developing resistance or intolerance to the drug, and some are due to kinase domain mutations, while others may have other yet unexplained reasons for suboptimal response. Continuous monitoring is mandatory in the care of CML patients, to aid early detection of suboptimal therapy outcomes, necessitating further molecular studies. Additionally, more work needs to be done to fully understand the mechanisms for these therapy failures in Nigerian CML patients.


Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; imatinib; nilotinib; Polymerase Chain Reaction; mutation; Drug Resistance.

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میز اداری صندلی مدیریتی صندلی اداری تبلیغات کلیکی میز تلویزیون پاراگلایدر آگهی رایگان محسن چاوشی مسیح و آرش آهنگ جدید دانلود آهنگ جدید خرید اینترنتی عکس بازیگران اطفار عکس بازیگران