Abstract：
:Imatinib (Gleevec) (formerly STI571) competitively targets the adenosine 5-triphosphate (ATP) binding site of the kinase domain of ABL and was recently approved for the treatment of chronic myeloid leukemia (CML). Point mutations occurring in the kinase domain of BCR-ABL have been identified as a cause of imatinib resistance. These mutations can be categorized into two groups: (1) mutations directly impairing the binding of imatinib but not ATP, and (2) mutations occurring in the ATP phosphate binding loop (P loop) or activation loop preventing the kinase to achieve conformation required for imatinib binding. Functional analysis of mutant BCR-ABL alleles in vitro has demonstrated four mutations (Q252H, F317L,M351T, E355G) to confer moderate resistance to imatinib, while T315I-, E255K-, Y253F-, and G250E-expressing cells are markedly resistant. Assay sensitivities and patient selection will affect the frequency of mutation detection. Another possible explanation for imatinib resistance is that mutated BCR-ABL-expressing cells might pre-exist the onset of treatment at levels below threshold detection (<20%), then expand under selective pressure of imatinib treatment. Rare mutated cells were identified using a very sensitive allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) assay in pretreatment samples of five CML patients supporting the theory that point mutations pre-existed imatinib treatment. Imatinib-resistant patients may benefit from molecular genotyping so mutations can be identified and clinical therapy adjusted accordingly.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Roche-Lestienne C,Preudhomme Cdoi
10.1053/shem.2003.50046subject
Has Abstractpub_date
2003-04-01 00:00:00pages
80-2issue
2 Suppl 2eissn
0037-1963issn
1532-8686pii
S0037196303000799journal_volume
40pub_type
杂志文章,评审abstract：:While cure rates of over 80% are achieved in contemporary pediatric acute lymphoblastic leukemia (ALL) protocols, most adults with ALL succumb to their disease, and little progress has been made in the treatment of refractory and relapsed ALL. Moreover, the burden of therapy is high in a significant number of newly di...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2009-01-01 00:00:00
abstract：:Idiopathic thrombocytopenic purpura (ITP) is an illness of primary acquired thrombocytopenia occurring in the absence of marrow failure. Splenectomy was first used as a treatment for ITP in 1913. However, with the realization that opsonin (critical for the optimal killing of invasive micro-organisms by white blood cel...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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journal_title：Seminars in hematology
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2018-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2004.01.002
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journal_title：Seminars in hematology
pub_type： 杂志文章
doi：10.1053/j.seminhematol.2016.04.019
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(01)90103-9
更新日期：2001-04-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1983-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1997-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1998-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2003.09.006
更新日期：2003-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2014-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1988-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1990-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1999-01-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1998-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2010-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2004.05.002
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journal_title：Seminars in hematology
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2012-01-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
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更新日期：2013-01-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(03)00135-5
更新日期：2003-07-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(00)90055-6
更新日期：2000-10-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2008.03.013
更新日期：2008-04-01 00:00:00
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journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(00)90094-5
更新日期：2000-07-01 00:00:00
abstract：:Two membrane proteins express the antigens that comprise the Kell blood group system. A single antigen, Kx, is carried on XK, a 440-amino acid protein that spans the membrane 10 times, and more than 20 antigens reside on Kell, a 93-kd, type II glycoprotein. XK and Kell are linked, close to the membrane surface, by a s...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(00)90036-2
更新日期：2000-04-01 00:00:00
abstract：:Trauma is rapidly replacing stroke and cardiovascular disease as a leading cause of death in Western countries such as the United States, and almost a third (30%) of trauma deaths are due to blood loss. Although the new intervention strategies that have been developed and adopted by emergency care staff have reduced t...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2003.11.009
更新日期：2004-01-01 00:00:00
