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

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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	Mutation_BCR-ABL1_Razga_Racil.pdf
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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