Clinically Actionable Mutations Identified in Korean Patients with High-Risk Acute Lymphoblastic Leukemia

Date 20 October 2018
Event ESMO 2018 Congress
Session Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Topics Leukaemia
Presenter Kyoung-Jin Park
Citation Annals of Oncology (2018) 29 (suppl_8): viii359-viii371. 10.1093/annonc/mdy286
Authors K. Park, I. Kim
  • Department Of Laboratory Medicine, Pusan National University Yangsan Hospital, 626-770 - Yangsan/KR



Identification of clinically actionable mutations in cancer is essential for catalyzing precision oncology based on risk stratification. Currently, little is known about the mutation profile of high-risk acute lymphoblastic leukemia (ALL) in Korean patients. We aimed to develop a multigene panel for ALL and to investigate clinically actionable mutations in the Korean patients with high-risk ALL.


We developed a multigene panel targeting 102 genes with diagnostic, prognostic, or therapeutic significance in ALL and validated it using reference materials and clinical samples. The mutation analyses were done in a total of 18 patients with high-risk ALL {T lymphoblastic leukemia (T-ALL, n = 7), B lymphoblastic leukemia in relapse (relapsed B-ALL, n = 5), and Philadelphia chromosome-positive ALL (Ph+ ALL, n = 6)}. High-risk ALL was categorized based on clinical findings and laboratory tests including immunophenotyping, chromosome analyses, fluorescence in situ hybridization, and RT-PCR. Clinically actionable mutations were selected based on a four-tiered system recommended by Association for Molecular Pathology in 2017.


A total of 28 clinically actionable mutations including 6 novel mutations were identified in 83% of the patients. The most frequent alterations in Korean patients were loss of function mutations of KMT2C (78%), followed by mutations of NOTCH1 (17%) and SUZ12 (11%). There is no difference in the frequency of KMT2C mutation among T-ALL, relapsed B-ALL, and Ph+ ALL, while mutations in NOTCH1 and SUZ12 were observed only in T-ALL. Additional 8 genes including NT5C2 and KRAS were mutated. Furthermore, potential germline pathogenic variants were discovered in 3 patients including one previously diagnosed as neurofibromatosis type 1.


This study showed that KMT2C mutations were recurrently observed in Korean patients with high-risk ALL. The KMT2C mutation status could be an effective risk stratification strategy for Korean patients with ALL. This study provides clinically actionable mutational portrait of high-risk ALL, albeit in a limited number of patients and gives novel insight into genetic heterogeneity of the disease.

Clinical trial identification

Legal entity responsible for the study

Pusan National University Yangsan Hospital Institutional Review Board.


Biomedical Research Institute in Pusan National University Yangsan Hospital.

Editorial Acknowledgement


All authors have declared no conflicts of interest.