Differences in Variants in the Structural Domain of BCR-ABL1 Kinase between Chinese Han and Minority Patients with Chronic Myeloid Leukemia by Sanger Sequencing and Next-Generation Sequencing

Cytogenet Genome Res. 2022;162(4):201-206. doi: 10.1159/000524706. Epub 2022 Sep 27.


This study aimed to detect differences in BCR-ABL1 kinase domain (KD) variants in patients with chronic myeloid leukemia (CML) who have been warned and failed in tyrosine kinase inhibitor (TKI) treatment among Chinese Han and ethnic minorities through Sanger sequencing (SS) and next-generation sequencing (NGS), and analyze the difference between SS and NGS detection. Peripheral blood samples from 51 CML patients with warning and failure of TKI therapy were analyzed using SS and NGS, and the detection differences between both sequencing types were compared. BCR-ABL1 KD variants were found in 23.53% of the cohort, including 7 Han Chinese (58.33%) and 5 ethnic minority cases (41.67%). Y253H, F317L, M244V, D276G, F359I, L387F, E459K, E255K, T315I, M351V, and heterozygous insertional mutated genes (ABL1 c.1068_1070dup) were detected. Comparison of the two sequencing assays revealed that NGS could detect compound variants and low frequency variants that were not detected by SS. More compound variants were detected in Han patients than in ethnic minority patients. In conclusion, there is no significant difference in BCR-ABL1 KD mutations between Han and ethnic minority patients. NGS has a higher mutation detection rate than SS, and can detect compound variants and genes with lower mutation frequency that are not detected by SS.

Keywords: Chronic myeloid leukemia; Compound variants; Ethnic minority; Han Chinese; Next-generation sequencing; Sanger sequencing.

MeSH terms

  • Drug Resistance, Neoplasm / genetics
  • East Asian People
  • Ethnicity
  • Fusion Proteins, bcr-abl* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Minority Groups
  • Mutation


  • Fusion Proteins, bcr-abl