Philadelphia chromosome-negative B-cell acute lymphoblastic leukaemia with kinase fusions in Taiwan.

Abstract

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions.

• Authors: Yin-Chen Hsu, Chih-Hsiang Yu, Yan-Ming Chen, Kathryn G Roberts, Yu-Ling Ni, Kai-Hsin Lin, Shiann-Tarng Jou, Meng-Yao Lu, Shu-Huey Chen, Kang-Hsi Wu, Hsiu-Hao Chang, Dong-Tsamn Lin, Shu-Wha Lin, Ze-Shiang Lin, Wei-Tzu Chiu, Chia-Ching Chang, Bing-Ching Ho, Charles G Mullighan, Sung-Liang Yu, Yung-Li Yang
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 5802 (03 11 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33707599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Heavy Chains
• Neoplasm Proteins
• Oncogene Proteins, Fusion
• Protein Kinases

Topics

• Base Sequence
• Child
• Child, Preschool
• Cohort Studies
• Female
• Gene Deletion
• Gene Rearrangement (genetics)
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Infant
• Male
• Neoplasm Proteins (metabolism)
• Oncogene Proteins, Fusion (metabolism)
• Philadelphia Chromosome
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (metabolism)
• Progression-Free Survival
• Protein Kinases (metabolism)
• Taiwan