Barańska Marta, Lewandowski Krzysztof, Gniot Michał, Iwoła Małgorzata, Lewandowska Maria, Komarnicki Mieczysław
Department of Hematology, Poznan University of Medical Sciences, Poznań, Poland.
J Appl Genet. 2008;49(2):201-3. doi: 10.1007/BF03195613.
Point mutations of bcr-abl tyrosine kinase are the most frequent causes of imatinib resistance in chronic myeloid leukaemia (CML) patients. In most CML cases with BCR-ABL mutations leading to imatinib resistance the second generation of tyrosine kinase inhibitors (TKI- e.g. nilotinib or dasatinib) may be effective. Here, we report a case of a CML patient who during imatinib treatment did not obtain clinical and cytogenetic response within 12 months of therapy. The sequencing of BCR-ABL kinase domains was performed and revealed the presence of a F359I point mutation (TTC-to-ATC nucleotide change leading to Phe-to-Ile amino acid substitution). After 1 month of nilotinib therapy a rapid progression of clinical symptoms was observed. In the presence of the F359I point mutation only dasatinib treatment overcame imatinib and nilotinib resistance.
bcr-abl酪氨酸激酶的点突变是慢性粒细胞白血病（CML）患者伊马替尼耐药最常见的原因。在大多数因BCR-ABL突变导致伊马替尼耐药的CML病例中，第二代酪氨酸激酶抑制剂（TKI，如尼罗替尼或达沙替尼）可能有效。在此，我们报告1例CML患者，其在伊马替尼治疗期间，治疗12个月内未获得临床和细胞遗传学反应。对BCR-ABL激酶结构域进行测序，发现存在F359I点突变（TTC到ATC的核苷酸变化，导致苯丙氨酸到异亮氨酸的氨基酸替换）。尼罗替尼治疗1个月后，观察到临床症状迅速进展。在存在F359I点突变的情况下，只有达沙替尼治疗克服了伊马替尼和尼罗替尼耐药。
