期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 193, 期 2, 页码 271-279出版社
WILEY
DOI: 10.1111/bjh.17301
关键词
acute lymphoblastic leukemia; BCR‐ ABL1; mutations; tyrosine kinase inhibitors; NGS
类别
Our study compared the results of Sanger sequencing and next-generation sequencing in Ph+ ALL patients, revealing that NGS provides more accurate and sensitive detection of mutations, particularly in cases of hematologic resistance and minimal residual disease.
BCR-ABL1 kinase domain mutation testing in tyrosine kinase inhibitor (TKI)-resistant Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) patients is routinely performed by Sanger sequencing (SS). Recently, next-generation sequencing (NGS)-based approaches have been developed that afford greater sensitivity and straightforward discrimination between compound and polyclonal mutations. We performed a study to compare the results of SS and NGS in a consecutive cohort of 171 Ph+ ALL patients. At diagnosis, 0/44 and 3/44 patients were positive for mutations by SS and NGS respectively. Out of 47 patients with haematologic resistance, 45 had mutations according to both methods, but in 25 patients NGS revealed additional mutations undetectable by SS. Out of 80 patients in complete haematologic response but with BCR-ABL1 >= 0 center dot 1%, 28 (35%) and 52 (65%) were positive by SS and NGS respectively. Moreover, in 12 patients positive by SS, NGS detected additional mutations. NGS resolved clonal complexity in 34 patients with multiple mutations at the same or different codons and identified 35 compound mutations. Our study demonstrates that, in Ph+ ALL on TKI therapy, NGS enables more accurate assessment of mutation status both in patients who fail therapy and in patients with minimal residual disease above 0 center dot 1%.
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