Abstract
Wilm’s tumor 1 (WT1), a zinc-finger transcription factor and an epigenetic modifier, is frequently overexpressed in several hematologic disorders and solid tumors, and it has been proposed as diagnostic and prognostic marker of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the exact role of WT1 in leukemogenesis and disease progression remains unclear. In this real-world evidence retrospective study, we investigated prognostic role of WT1-mRNA expression levels in AML and MDS patients and correlations with complete blood counts, flow cytometry counts, and molecular features. A total of 71 patients (AML, n = 46; and MDS, n = 25) were included in this study, and WT1 levels were assessed at diagnosis, during treatment and follow-up. We showed that WT1 expression levels were inversely correlated with normal hemopoiesis in both AML and MDS, and positively associated with blast counts. Flow cytometry was more sensitive and specific in distinguishing normal myeloid cells from neoplastic counterpart even just using linear parameters and CD45 expression. Moreover, we showed that a simple integrated approach combining blast counts by flow cytometry, FLT3 mutational status, and WT1 expression levels might be a useful tool for a better prognostic definition in both AML and MDS patients.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous group of clonal aggressive hematologic malignancies characterized by differentiation block and increased proliferation of neoplastic cells of myeloid origins [1]
Whether to investigate associations between Wilm’s tumor 1 (WT1)-mRNA levels and acute myeloid leukemia (AML) disease severity and prognosis, WT1 expression was assessed at diagnosis, during therapy, and follow-up, and levels were correlated with complete blood counts (CBCs) and flow cytometer counts
Percentage of bone marrow (BM) blasts identified by light microscopy or flow cytometry was correlated with normalized WT1 expression (Figure 1)
Summary
Acute myeloid leukemia (AML) is a heterogeneous group of clonal aggressive hematologic malignancies characterized by differentiation block and increased proliferation of neoplastic cells of myeloid origins [1]. MDS are a group of clonal premalignant hematological diseases characterized by ineffective hematopoiesis, progressive PB cytopenias, increased risk of developing AML, and poor overall survival (OS) [2]. MDS are heterogeneous in clinical presentation, cytogenetics and molecular signatures resulting in various outcomes with OS ranging from 5 years to 9 months [5]. Several genetic alterations frequently found in MDS can be present in other hematological disorders and in healthy individuals because clonal hematopoiesis is commonly seen with aging [6,7]
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