ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis.
Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.
Sacha
Tomasz
T
Department of Haematology, Jagiellonian University Medical College, Cracow, Poland. mmsacha@cyf-kr.edu.pl
Hochhaus
Andreas
A
Hanfstein
Benjamin
B
Müller
Martin C
MC
Rudzki
Zbigniew
Z
Czopek
Jacek
J
Wolska-Smoleń
Teresa
T
Czekalska
Sylwia
S
Salamanchuk
Zoriana
Z
Jakóbczyk
Malgorzata
M
Skotnicki
Aleksander B
AB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001549:Benzamides; D001752:Blast Crisis / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010879:Piperazines / Q000627:therapeutic use*; D017354:Point Mutation / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D012689:Sequence Homology, Nucleic Acid
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D000255:Adenosine Triphosphate; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl