Simultaneous detection of ABL 1 mutation and IKZF 1 deletion in Philadelphia chromosome‐positive acute lymphoblastic leukemia using a customized target enrichment system panel

Recent clinical outcomes of pediatric Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL ) vastly improved owing to tyrosine kinase inhibitor ( TKI ). However, the genetic status would be different in each case with ABL 1 gene mutation or copy number variants ( CNV s) such as IKZF 1 deletion. In particular, the TKI resistant clone with ABL 1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNV s is necessary. Methods We evaluated a next‐generation sequencing ( NGS )‐based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNV s. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ ALL patients. Results Mono‐allelic IKZF 1 deletions were found in 4 patients at diagnosis. Furthermore, the mono‐allelic deletions were found in exons of RB 1 , EBF 1 , PAX 5 and ETV 6 genes. Bi‐allelic deletions were detected in CDKN 2A and CDKN 2B genes in 1 patient. ABL 1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation‐dependent probe amplification ( MLPA ) method or Sanger sequence. Conclusion Next‐generation sequencing‐based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNV s in pediatric Ph+ ALL simultaneously, and its results seem comparable with those of other methods.