Publications by authors named "P van der Valk"
Mutation of DNMT3A, encoding a de novo methyltransferase essential for cytosine methylation, is a common early event in clonal hematopoiesis (CH) and adult acute myeloid leukemia (AML). Spontaneous deamination of methylated cytosines damages DNA, which is repaired by the base excision repair (BER) enzymes MBD4 and TDG. Congenital MBD4-deficiency has been linked to early-onset CH and AML, and is marked by exceedingly high levels of DNA damage and mutation of DNMT3A.
View Article and Find Full Text PDFMutations in the Nucleophosmin-1 (NPM1) gene are among the most common molecular aberrations in acute myeloid leukemia (AML). Various studies have established mutant NPM1 (mNPM1) as a faithful molecular measurable residual disease (MRD) marker with prognostic significance. Assessment of prognostic mNPM1 is included in the European LeukemiaNet (ELN) recommendations on MRD detection in AML.
View Article and Find Full Text PDFKMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM.
View Article and Find Full Text PDFApoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome.
View Article and Find Full Text PDFArticle Synopsis
- - BCR::ABL1 digital PCR is a highly sensitive and precise method for measuring deep molecular responses in chronic myeloid leukemia, outperforming traditional qPCR, especially in predicting successful treatment-free remission.
- - In a study with 168 patient samples, digital PCR demonstrated better detection capabilities, quantifying BCR::ABL1 in 68% of cases that were below the detection limit of qPCR, which required a high number of transcripts.
- - The technique also allowed for differentiation between BCR::ABL1 transcript types, making it a practical and effective option for clinical use in monitoring treatment responses.