Prognostic Role of Postinduction Minimal Residual Disease and Myeloid Sarcoma Type Extramedullary Involvement in Pediatric RUNX1-RUNX1T1 (+) Acute Myeloid Leukemia.
AML with mutated <i>NPM1</i> and AML with myelodysplasia-related changes comprised the oldest patients, whereas AML with <i>RUNX1-RUNX1T1</i> included the youngest patients.
Based on these 293 genes, the cyclooxygenase (COX), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR) pathways were predicted to be specifically activated in AMLs with <i>RUNX1-RUNX1T1</i> fusion.
Interestingly, in comparison with AML1-ETO binding in acute myeloid leukemias (AMLs), we found significantly distinct genomic distribution and differential expression for RUNX1mut of genes such as <i>TCF4</i>, <i>MEIS1</i>, and <i>HMGA2</i> that may potentially contribute to the underlying difference in clinical outcomes between RUNX1mut and AML1-ETO patients.
Oncogenic fusion protein RUNX1-ETO is the product of the t(8;21) translocation, responsible for the most common cytogenetic subtype of acute myeloid leukemia.
The t(7;21)(p22;q22) resulting in RUNX1-USP42 fusion, is a rare but recurrent cytogenetic abnormality associated with acute myeloid leukemia (AML) and myelodysplastic syndromes.
Negative CD19 expression is associated with inferior relapse-free survival in children with RUNX1-RUNX1T1-positive acute myeloid leukaemia: results from the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.
The demonstration of RUNX1 mutation in both non-LCH and AML bone marrow specimens at differing time points is suggestive of a biologic association of both distinct disease entities.
In conclusion, we show that gene expression profiling of RUNX1 knock-down or mutated MK provides a suitable approach to identify novel RUNX1 targets, among which downregulation of <i>TREML1</i> and <i>ITGA2</i> clearly contribute to the platelet phenotype of familial platelet disorder with predisposition to AML.
Recent studies identified a recurrent mutational hotspot, R222G, in DHX15 in ~ 6% of acute myeloid leukemia (AML) patients that carry the fusion protein RUNX1-RUNX1T1 produced by t (8;21) (q22;q22).
GATA2 and RUNX1 deficiency is not associated with host susceptibility to DNA damage, and therefore, conventional treatment strategies for MDS and AML can be used.
Moreover, treatment with BET protein inhibitor or degrader (BET-proteolysis targeting chimera) repressed RUNX1 and its targets, inducing apoptosis and improving survival of mice engrafted with AML expressing mtRUNX1.
The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies.