Your browser doesn't support javascript.
loading
Clonogenic assays improve determination of variant allele frequency of driver mutations in myeloproliferative neoplasms.
Kalmer, Milena; Pannen, Kristina; Lemanzyk, Rebecca; Wirths, Chiara; Baumeister, Julian; Maurer, Angela; Kricheldorf, Kim; Schifflers, Joelle; Gezer, Deniz; Isfort, Susanne; Brümmendorf, Tim H; Koschmieder, Steffen; Chatain, Nicolas.
Afiliación
  • Kalmer M; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Pannen K; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Lemanzyk R; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Wirths C; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Baumeister J; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Maurer A; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Kricheldorf K; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Schifflers J; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Gezer D; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Isfort S; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Brümmendorf TH; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • Koschmieder S; Center for Integrated Oncology, Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
  • Chatain N; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Ann Hematol ; 101(12): 2655-2663, 2022 Dec.
Article en En | MEDLINE | ID: mdl-36269400
Molecular diagnostics moves more into focus as technology advances. In patients with myeloproliferative neoplasms (MPN), identification and monitoring of the driver mutations have become an integral part of diagnosis and monitoring of the disease. In some patients, none of the known driver mutations (JAK2V617F, CALR, MPL) is found, and they are termed "triple negative" (TN). Also, whole-blood variant allele frequency (VAF) of driver mutations may not adequately reflect the VAF in the stem cells driving the disease. We reasoned that colony forming unit (CFU) assay-derived clonogenic cells may be better suited than next-generation sequencing (NGS) of whole blood to detect driver mutations in TN patients and to provide a VAF of disease-driving cells. We have included 59 patients carrying the most common driver mutations in the establishment or our model. Interestingly, cloning efficiency correlated with whole blood VAF (p = 0.0048), suggesting that the number of disease-driving cells correlated with VAF. Furthermore, the clonogenic VAF correlated significantly with the NGS VAF (p < 0.0001). This correlation was lost in patients with an NGS VAF <15%. Further analysis showed that in patients with a VAF <15% by NGS, clonogenic VAF was higher than NGS VAF (p = 0.003), suggesting an enrichment of low numbers of disease-driving cells in CFU assays. However, our approach did not enhance the identification of driver mutations in 5 TN patients. A significant correlation of lactate dehydrogenase (LDH) serum levels with both CFU- and NGS-derived VAF was found. Our results demonstrate that enrichment for clonogenic cells can improve the detection of MPN driver mutations in patients with low VAF and that LDH levels correlate with VAF.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Mieloproliferativos / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastornos Mieloproliferativos / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Ann Hematol Asunto de la revista: HEMATOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania