Prognostic Impact of BloodCopy Numbers Before Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia.

in HemaSphere by Madlen Jentzsch, Marius Bill, Juliane Grimm, Julia Schulz, Stefanie Beinicke, Janine Häntschel, Karoline Goldmann, Wolfram Pönisch, Georg-Nikolaus Franke, Vladan Vucinic, Michael Cross, Gerhard Behre, Thoralf Lange, Dietger Niederwieser, Sebastian Schwind

TLDR

  • The study looked at how well a gene called meningioma-1 is expressed in people with acute myeloid leukemia (AML). They found that people with high levels of meningioma-1 expression were more likely to have a relapse after a stem cell transplant. They also found that assessing the number of copies of the meningioma-1 gene in a person's blood before the transplant could help predict whether they would have a relapse. This study highlights the potential of using gene expression levels as a prognostic marker for relapse in AML patients.

Abstract

High expression of the leukemia-associated gene meningioma-1 () is frequently found at diagnosis of acute myeloid leukemia (AML) and associates with adverse outcomes. The presence of measurable residual disease (MRD) in complete remission (CR) indicates high risk of relapse and worse outcome in AML patients. However, the prognostic impact ofexpression levels as MRD marker has not been evaluated. Digital droplet polymerase chain reaction (ddPCR) is a novel technique allowing sensitive and specific absolute gene expression quantification. We retrospectively analyzed 124 AML patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in CR or CR with incomplete peripheral recovery. Absolutecopy numbers in peripheral blood were assessed prior to HSCT (median 7; range 0-29 days) using ddPCR. High pre-HSCT/Abelson murine leukemia viral oncogene homolog 1 gene () copy numbers associated with a higher cumulative incidence of relapse after HSCT and-in relapsing patients-shorter time to relapse. In multivariable analysis, high pre-HSCT/copy numbers remained an independent prognosticator for relapse after HSCT. Patients with the highest pre-HSCT/copy numbers also had the highest risk of relapse.copy number assessment also added prognostic information to nucleophosmin 1 gene () mutation- and brain and acute leukemia, cytoplasmic () and Wilm's tumor gene 1 () expression-based MRD evaluation. Our study demonstrates the feasibility of the novel ddPCR technique for/copy number assessment as a marker for MRD. Evaluation of/copy numbers allows the identification of patients at high risk of relapse, independently of other diagnostic risk factors and MRD markers.

Overview

  • The study focuses on the role of meningioma-1 gene expression in acute myeloid leukemia (AML) and its association with adverse outcomes. The methodology involves retrospective analysis of 124 AML patients who received allogeneic hematopoietic stem cell transplantation (HSCT) in CR or CR with incomplete peripheral recovery. The study uses digital droplet polymerase chain reaction (ddPCR) to assess absolute copy numbers of the meningioma-1 gene in peripheral blood prior to HSCT. The primary objective is to evaluate the prognostic impact of meningioma-1 gene expression levels as a marker for measurable residual disease (MRD) in AML patients.

Comparative Analysis & Findings

  • The study compares the outcomes observed in AML patients with high and low pre-HSCT/meningioma-1 gene copy numbers. The results show that high pre-HSCT/meningioma-1 gene copy numbers are associated with a higher cumulative incidence of relapse after HSCT and a shorter time to relapse in relapsing patients. In multivariable analysis, high pre-HSCT/meningioma-1 gene copy numbers remain an independent prognosticator for relapse after HSCT. The study also demonstrates that the assessment of meningioma-1 gene copy numbers adds prognostic information to other diagnostic risk factors and MRD markers.

Implications and Future Directions

  • The study's findings suggest that meningioma-1 gene expression levels can be used as a prognostic marker for relapse in AML patients. The study highlights the feasibility of using digital droplet polymerase chain reaction (ddPCR) for absolute copy number assessment as a marker for measurable residual disease (MRD). Future research could further explore the use of meningioma-1 gene expression levels as a prognostic marker in AML and evaluate its performance in predicting relapse compared to other MRD markers. Additionally, future studies could investigate the potential of using meningioma-1 gene expression levels as a target for therapeutic interventions in AML.
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