Abstract
Novel recurrent fusion gene types such as zinc finger protein 384 (ZNF384) fusions have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the application of next-generation sequencing technologies. However, the comprehensive large-scale clinical cohort study for clarifying their prognostic significance remains scarce to date. A total of 242 consecutive adult Ph-negative BCP-ALL patients treated in our institute were retrospectively screened ZNF384 fusions at diagnosis by multiplex real time quantitative PCR. ZNF384 fusions were identified in 47 patients (19.4%) and all belonged to B-other ALL (having no high hyperdiploid karyotype, BCR-ABL1, TCF3-PBX1, ETV6-RUNX1, or MLL rearrangement). In the whole cohort, patients with ZNF384 fusions had significantly higher 3-year relapse-free-survival (RFS) and tended to have a higher 3-year overall survival (OS) than those with no ZNF384 fusions (80.1% vs. 52.5%, P = 0.013; 67.6% vs. 54.0%, P = 0.10). For patients receiving chemotherapy alone and received allogeneic-hematologic stem cell transplantation (allo-HSCT) were censored at the time of transplantation, patients with ZNF384 fusions had both similar RFS and similar OS to B-other ALL patients with no ZNF384 fusions (RFS: P =0.94 and 0.30; OS: P =0.94 and 0.51). For patients receiving transplantation, those with ZNF384 fusions had significantly higher 3-year RFS than B-other ALL patients with no ZNF384 fusions and their OS were similar (P = 0.022 and 0.24). Only two of 31 patients with ZNF384 fusions and receiving allo-HSCT relapsed, individually occurred 66.8 and 69.8 months after transplantation. Therefore, ZNF384 fusion is common in adult BCP-ALL, which may define a new group from BCP-ALL containing no classical fusion transcript with better prognosis through receiving allo-HSCT.
Highlights
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a molecular and cytogenetic heterogeneous disease
Despite the identification of novel recurrent fusion genes in BCPALL with the application of next-generation sequencing technologies, the comprehensive large-scale clinical cohort study for clarifying their prognostic significance remains scarce to date
By performing real time quantitative polymerase chain reaction (RQ-PCR) to screen zinc finger protein 384 (ZNF384) fusions in 242 consecutive adult Ph-negative BCP-ALL cases at diagnosis, we found that the ZNF384 fusions was related to higher RFS in the whole cohort
Summary
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a molecular and cytogenetic heterogeneous disease. Oncogenic gene fusions induced by chromosomal rearrangements and specific aneuploidy patterns are the major hallmarks of BCPALL [1]. The aim of the identification of novel genomic abnormalities is to refine risk stratification to guide optimal treatment strategies and discover new therapies. The majority of published papers concerning the novel fusions of BCP-ALL focused on the identification of genomic lesions using new sequencing technologies, in which survival results were just showed briefly or not exhibited [2,3,4,5,6,7,8,9,10,11]. The clinical cohort study which comprehensively investigates the characteristics and the prognosis of the individual novel fusions remains scarce to date
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