Impact of clonal architecture on clinical course and prognosis in patients with myeloproliferative neoplasms

• DOI: 10.1101/2022.09.24.509318
• Publication Date: 2022-09-26T21:20:16Z
• Authors: Damien Luque Paz; Michael S. Bader; Ronny Nienhold; Shivam Rai; Tiago Almeida Fon...; Jan Stetka; Hui Hao-Shen; Gabi Mild-Schneider; Jakob R. Passweg; Radek C. Skoda
• Keywords: COLD-PCR; clone (Java method)

Abstract Myeloproliferative neoplasms (MPNs) are caused by a somatic gain-of-function mutation in one of three “disease driver” genes JAK2, MPL or CALR . About half MPN patients also carry additional mutations that modify the clinical course. The order acquisition these gene has been proposed to influence phenotype and evolution disease. We studied 50 JAK2 -V617F-positive who carried at least determined clonal architecture their hematopoiesis sequencing DNA from single cell derived colonies. In 22 we side-by-side applied Tapestri single-cell (scDNAseq) with cells same blood sample. architectures two methods showed good overall concordance. scDNAseq higher sensitivity for low variant allele fraction, but had more difficulties distinguishing between heterozygous homozygous mutations. By unsupervised analysis data all defined 4 distinct clusters differed mutations, complexity subclonal structure. Cluster 4, characterized complex structure without preferred acquisition, correlated reduced survival, multivariate represented risk factor independent subtype age diagnosis. Our results suggest deciphering multiple can improve molecular prognostic stratification until now was primarily based on number type