ZNF384 fusion transcript levels for measurable residual disease monitoring in adult B-cell acute lymphoblastic leukemia

Hematol Oncol. 2024 Jan;42(1):e3251. doi: 10.1002/hon.3251.

Abstract

Zinc finger protein 384 (ZNF384) rearrangement defined a novel subtype of B-cell acute lymphoblastic leukemia (B-ALL). The prognostic significance of ZNF384 fusion transcript levels represented measurable residual disease remains to be explored. ZNF384 fusions were screened out in 57 adult B-ALL patients at diagnosis by real-time quantitative polymerase chain reaction and their transcript levels were serially monitored during treatment. The reduction of ZNF384 fusion transcript levels at the time of achieving complete remission had no significant impact on survival, whereas its ≥2.5-log reduction were significantly associated with higher relapse free survival (RFS) and overall survival (OS) rates after course 1 consolidation (p = 0.022 and = 0.0083) and course 2 consolidation (p = 0.0025 and = 0.0008). Compared with chemotherapy alone, allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS of patients with <2.5-log reduction after course 1 consolidation (p < 0.0001 and = 0.0002) and course 2 consolidation (p = 0.0003 and = 0.019), whereas exerted no significant effects in patients with ≥2.5-log reduction (all p > 0.05). ZNF384 fusion transcript levels after course 1 and course 2 consolidation strongly predict relapse and survival and may guide whether receiving allo-HSCT in adult B-ALL.

Keywords: B-cell acute lymphoblastic leukemia; ZNF384; fusion genes; measurable residual disease; prognosis.

MeSH terms

  • Adult
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Neoplasm, Residual / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Prognosis
  • Recurrence
  • Trans-Activators / metabolism
  • Trans-Activators / therapeutic use
  • Transcription Factors

Substances

  • Transcription Factors
  • ZNF384 protein, human
  • Trans-Activators