Publication details

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 JURČEK Tomáš JEZISKOVA Ivana ŽÁČKOVÁ Daniela DVOŘÁKOVÁ Dana BORSKÝ Marek MAYER Jiří RÁČIL Zdeněk

Year of publication 2012
Type Article in Periodical
Magazine / Source Molecular Diagnosis & Therapy
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://www.ncbi.nlm.nih.gov/pubmed/22489663
Doi http://dx.doi.org/10.2165/11632420-000000000-00000.
Field Oncology and hematology
Keywords CHRONIC MYELOID-LEUKEMIA; IMATINIB RESISTANCE; ABL MUTATIONS; TRANSCRIPTS; PROGENITORS; INHIBITOR; ASSAY
Attached files
Description 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.
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