RÁZGA, Filip, Tomáš JURČEK, Ivana JEZISKOVA, Daniela ŽÁČKOVÁ, Dana DVOŘÁKOVÁ, Marek BORSKÝ, Jiří MAYER and Zdeněk RÁČIL. Analysis of Mutations in the BCR-ABL1 Kinase Domain, Using Direct Sequencing Detection of the T315I Mutation in Bone Marrow CD34+Cells of a Patient with Chronic Myelogenous Leukemia 6 Months Prior to its Emergence in Peripheral Blood. Molecular Diagnosis & Therapy. AUCKLAND: ADIS INT LTD, 2012, vol. 16, No 3, p. 163-166. ISSN 1177-1062. Available from: https://dx.doi.org/10.2165/11632420-000000000-00000.
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Basic information
Original name Analysis of Mutations in the BCR-ABL1 Kinase Domain, Using Direct Sequencing Detection of the T315I Mutation in Bone Marrow CD34+Cells of a Patient with Chronic Myelogenous Leukemia 6 Months Prior to its Emergence in Peripheral Blood
Authors RÁZGA, Filip (703 Slovakia, guarantor, belonging to the institution), Tomáš JURČEK (203 Czech Republic, belonging to the institution), Ivana JEZISKOVA (203 Czech Republic), Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), Dana DVOŘÁKOVÁ (203 Czech Republic, belonging to the institution), Marek BORSKÝ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Zdeněk RÁČIL (203 Czech Republic, belonging to the institution).
Edition Molecular Diagnosis & Therapy, AUCKLAND, ADIS INT LTD, 2012, 1177-1062.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher New Zealand
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 1.692
RIV identification code RIV/00216224:14740/12:00060675
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.2165/11632420-000000000-00000.
UT WoS 000305442900004
Keywords in English CHRONIC MYELOID-LEUKEMIA; IMATINIB RESISTANCE; ABL MUTATIONS; TRANSCRIPTS; PROGENITORS; INHIBITOR; ASSAY
Tags ok, rivok
Tags International impact, Reviewed
Changed by Changed by: Olga Křížová, učo 56639. Changed: 23/4/2013 07:49.
Abstract
Background and Objective: It has been shown that the occurrence of the BCR-ABL1 T315I mutation leads to a very poor therapeutic outcome in chronic myelogenous leukemia (CM L) patients treated with tyrosine kinase inhibitors. Therefore, early detection of this mutation could potentially lead to early therapeutic intervention and a better prognosis with the ongoing treatment regimen. Methods: The detection of BCR-ABL1 kinase domain (KID) mutations was performed by direct sequencing of peripheral blood (PB), total bone marrow (BM), and BM CD34+ cells from a reported CML patient. Results: In this patient, the T315I mutation was detected in BM CD34+ cells 6 months prior to its emergence in PB, suggesting evolution and expansion of the T315I mutation clone, which most likely originated from more primitive CML cells. Conclusion: Our finding reflects the natural development of a T315I mutation within the hematopoietic system of the reported patient and indicates the importance of BCR-ABL1 mutation monitoring in more primitive cell populations. Considering the natural history of T315I development in this reported CM L case, we hypothesize that BCR-ABL1 KD mutations may be pre-concentrated in more primitive CM L cells, which subsequently expand into the PB. These findings may have future implications for the strategy used for detecting BCR-ABL1 mutations.
Links
MSM0021622430, plan (intention)Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie
Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies
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