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Next‐generation sequencing improves BCR‐ABL1 mutation detection in Philadelphia chromosome‐positive acute lymphoblastic leukaemia
Author(s) -
Soverini Simona,
Martelli Margherita,
Bavaro Luana,
De Benedittis Caterina,
Papayannidis Cristina,
Sartor Chiara,
Sorà Federica,
Albano Francesco,
Galimberti Sara,
Abruzzese Elisabetta,
Annunziata Mario,
Russo Sabina,
Stulle Manuela,
Imovilli Annalisa,
Bonifacio Massimiliano,
Maino Elena,
Stagno Fabio,
Maria Basilico Claudia,
Borlenghi Erika,
Fozza Claudio,
Mig Flavio,
Minari Roberta,
Stella Stefania,
Baccarani Michele,
Cavo Michele,
Martinelli Giovanni
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17301
Subject(s) - sanger sequencing , medicine , mutation , minimal residual disease , dna sequencing , philadelphia chromosome , oncology , dasatinib , cancer research , tyrosine kinase , genetics , gene , leukemia , biology , chromosomal translocation , receptor
Summary 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 ≥0·1%, 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 0·1%.