WT1 and TP53 as valuable diagnostic biomarkers for relapse after hematopoietic stem cell transplantation in acute myeloid leukemia.

BACKGROUND: Relapse following hematopoietic stem cell transplantation (HSCT) occurs relatively frequently and is a significant risk factor for mortality in patients with acute myeloid leukemia (AML). Early diagnosis is, therefore, of utmost importance and can provide valuable guidance for appropriate and timely intervention. Here, the diagnostic value of two molecular markers, Wilms tumor 1 (WT1) and tumor suppressor protein p53 (TP53), were studied. METHODS AND RESULTS: Twenty AML patients undergoing HSCT participated in this investigation. Some had relapsed following HSCT, while others were in remission. Peripheral blood (PB) and bone marrow (BM) samples were collected following relapse and remission. WT1 and TP53 messenger RNA (mRNA) expression was evaluated using reverse transcription-quantitative polymerase chain reaction (RT‒qPCR). The diagnostic value of genes was evaluated by utilizing receiver-operating characteristic (ROC) curve analysis. ROC analysis showed WT1 and TP53 as diagnostic markers for relapse after HSCT in AML patients. The mRNA expression level of WT1 was elevated in individuals who experienced relapse compared to those in a state of remission (p value < 0.01). Conversely, the expression level of TP53 mRNA was lower in individuals who had relapsed compared to those in remission (p value < 0.01). CONCLUSIONS: WT1 and TP53 possess the potential to serve as invaluable biomarkers in the identification of molecular relapse after HSCT in patients with AML. Further studies for a definitive conclusion are recommended.

Correlation of miR-155-5p, KRAS, and CREB Expression in Patients with Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer involving numerous aberrant genes and microRNAs. MiRNAs are non-coding sequences that have been proven to be players in the biological processes of various cancers. The present study is designed to illustrate the relationship between miR-155, KRAS, and CREB. METHODS: This case-control study was conducted on 21 patients with AML and 9 healthy individuals. The expressions of miR-155, KRAS, and CREB were measured using RT-PCR. Demographic data were extracted from the documents of individuals. SPSS and GraphPad Prism software were used to analyze the data. RESULTS: The expression of miR-155 in patients with AML was 35 times higher than in the control group (p < 0.0001). Also, CREB fold change increased by 1.92-fold in patients compared to the controls (p = 0.034), but no difference in KRAS was observed between the control and AML groups (p > 0.05). There was no change in miR-155, CREB, and KRAS expression based on gender, age, and blast percentage (p > 0.5). Nevertheless, there was a direct correlation between CREB and KRAS expressions (p = 0.0002). Our result showed that overexpression of CREB and KRAS would cause an increase in white blood cells (WBCs) (p = 0.001, 0.045 respectively), but there was no correlation between miR-155 with WBCs (p > 0.5). CONCLUSIONS: Our study revealed that miR-155 and CREB had overexpression compared to the control group.

Investigating the multifaceted cooperation of autophagy, PI3K/AKT signaling pathways, and INPP4B gene in de novo acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) has been the most prevalent form of acute leukemia among adults, and it has been associated with poor survival rates over the last four decades. Understanding the processes involved in leukemogenesis, particularly autophagy and signaling pathways, can provide critical insights into their roles in disease development, risk assessment, and potential therapeutic interventions. This study investigated gene expression changes, focusing on MAP1LC3B and BECN1, related to autophagy, as well as PI3KCA and AKT1 in the PI3K-AKT pathway, and INPP4B, which regulates this signaling cascade. METHODS: We collected blood samples from 21 AML patients and 9 healthy volunteers. Gene expression was analyzed through qPCR following RNA extraction and cDNA synthesis. Statistical analysis encompassed t-tests, ANOVA, and correlation coefficients. RESULTS: AML patients exhibited significantly increased MAP1LC3B gene expression (****P < 0.0001; fold change = 11.9) and significantly reduced levels of INPP4B (****P < 0.0001; fold change = 0.026), AKT1 (*P < 0.05; fold change = 0.59), and PI3KCA (****P < 0.0001; fold change = 0.16) compared to healthy controls. However, BECN1 gene expression did not significantly differ between the two groups. Additionally, noteworthy correlations were observed between INPP4B and BECN1 (r = 0.57; P = 0.006) and BECN1 and PI3KCA (r = 0.61; P = 0.003) in AML patients. CONCLUSIONS: This study highlights variations in leukemogenesis pathways, exemplified by increased MAP1LC3B expression and diminished expression of regulatory genes in specific AML cases. These findings contribute to our comprehension of the molecular mechanisms underlying AML and may inform future diagnostic and therapeutic approaches.