Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation.
Imatinib failure and response to dasatinib in a patient with chronic myeloid leukemia in blast crisis and a novel, nine-nucleotide BCR-ABL insertion mutation.
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DOI：
10.1038/bcj.2013.3
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发表时间：
2013-03-08
影响因子：
12.8
通讯作者：
von Bubnoff, N.
中科院分区：
文献类型：
--
作者：
Sigl, M.;Spoerl, S.;Schnittger, S.;Meissner, J.;Rummelt, C.;Peschel, C.;Duyster, J.;Ho, A. D.;von Bubnoff, N.
在慢性期慢性粒细胞白血病（CML）中，BCR-ABL激酶抑制剂伊马替尼在大多数病例中导致完全细胞遗传学缓解。对伊马替尼的耐药性与BCR-ABL激酶结构域突变相关，导致结构变化，阻止伊马替尼结合。1在伊马替尼治疗失败的情况下，第二代BCR-ABL激酶抑制剂如达沙替尼或尼洛替尼在CML中表现出活性。2这两种药物都能够抑制伊马替尼耐药的BCR-ABL突变形式。3大多数介导抑制剂耐药的BCR-ABL基因突变是点突变，取代了单个核苷酸。剪接突变BCR-ABL导致删除或插入的核苷酸延伸很少被描述。4在这里，我们报告了一名CML患者在伊马替尼治疗失败后发生急变，并使用达沙替尼进行二线治疗，该患者携带迄今为止未描述的p.K294S_insFPQ突变（g. 68009_68010ins GTTTCCCTC）。一名37岁女性患者最初表现为不适，淋巴结肿大和脾肿大。她的白色血细胞计数为122.7/nl，原始细胞占47%。骨髓形态显示80%原始细胞浸润。免疫表型分析显示CD 34、HLA-DR、CD 19、CD 10、TdT和cyCD 22的表达。费城染色体阳性
In chronic phase chronic myeloid leukemia (CML), the BCR-ABL kinase inhibitor imatinib leads to complete cytogenetic responses in the majority of cases. Resistance towards imatinib is associated with BCR-ABL kinase domain mutations, leading to structural changes that prevent imatinib from binding. 1 In cases of failure towards imatinib treatment, second generation BCR-ABL kinase inhibitors such as dasatinib or nilotinib have demonstrated activity in CML. 2 Both drugs are capable of suppressing imatinib-resistant, mutant forms of BCR-ABL. 3 Most of the mutations in the BCR-ABL gene mediating inhibitor resistance are point mutations, replacing single nucleotides. Splice mutations in BCR-ABL leading to deletion or insertion of nucleotide stretches have rarely been described. 4 Here, we report on a patient with CML in blast crisis after imatinib failure and second-line treatment with dasatinib harboring a so far undescribed p. K294S_insFPQ mutation (g. 68009_68010ins GTTTCCCTC). A 37-year-old female patient initially presented with malaise, lymphadenopathy and splenomegaly. Her white blood cell count was 122.7/nl with 47% blasts. Bone marrow morphology showed 80% blast infiltration. Immunophenotyping revealed expression of CD34, HLA-DR, CD19, CD10, TdT and cyCD22. A Philadelphia chromosome-positive
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影响因子：
64.5
作者：
Azam, M;Latek, RR;Daley, GQ
通讯作者：
Daley, GQ
影响因子：
50.3
作者：
Weisberg, E;Manley, PW;Griffin, JD
通讯作者：
Griffin, JD
影响因子：
158.5
作者：
Kantarjian, Hagop;Giles, Francis;Ottmann, Oliver G.
通讯作者：
Ottmann, Oliver G.
影响因子：
11.4
作者：
Hochhaus, A.;Baccarani, M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
2.1
作者：
Sakai, Katsuya;Ishikawa, Yuichi;Kiyoi, Hitoshi
通讯作者：
Kiyoi, Hitoshi