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Mutation in the ATP‐binding site of BCR‐ABL in a patient with chronic myeloid leukaemia with increasing resistance to STI571
Author(s) -
Barthe Christophe,
Gharbi Mariejosée,
Lagarde Valérie,
Chollet Claudine,
ConyMakhoul Pascale,
Reiffers Josy,
Goldman John M.,
Melo Junia V.,
Mahon François Xavier
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03708.x
Subject(s) - imatinib mesylate , tyrosine kinase , abl , myeloid leukemia , protein kinase domain , imatinib , point mutation , cancer research , tyrosine kinase inhibitor , mutation , philadelphia chromosome , biology , medicine , chromosomal translocation , genetics , receptor , mutant , gene , cancer
Summary. The Abl kinase inhibitor STI571 (imatinib mesylate) induces haematological remissions in many patients with chronic myeloid leukaemia (CML) but advanced stage CML usually becomes resistant to STI571. We describe a patient in whom progressive resistance to STI571 correlated with the appearance of a mutation in the Bcr‐Abl kinase domain. This was a G to A transition that resulted in a glutamic acid to lysine substitution at position 255 (E255K) in the Abl type 1a protein. We suggest that the acquisition of point‐mutations in the tyrosine kinase domain of Bcr‐Abl may cause progressive clinical resistance to STI571.