2013 - 2017
Subclone Expansion and Evolution in Ph+ CML and other MPN
The project part leader, Thomas Lion, has a long-lasting interest in Ph+ CML and is well known and well-embedded in the scientific community. Early in his career, he developed robust technologies for the MRD detection in CML. Since then, his lab and team are a well-known top reference center for BCR/ABL quantification, and well known for their innovative research efforts. During the past few years, Thomas established methodologies sufficient for the reliable quantification of BCR/ABL mutant-bearing CML subclones by employing a ligase-dependent PCR assay.
Using patient samples, this technique was found to represent a “next-generation” technology for the measurement of evolution, expansion, and depletion of LSC-derived (naturally persistent) subclones in Ph+ CML during treatment with BCR/ABL TKI. Thomas Lion is head of the Division of Molecular Diagnostics at the Children’s Cancer Research Institute (CCRI) Vienna, and Medical Director of LabDia Diagnostics (Vienna, Austria). In the project, the group examined and defined what molecular lesions and aberration profiles contribute to or even induce subclone evolution and subclone expansion in Ph+ CML. A long-term goal was to extend these analyses to Ph- MPN.
Project #05 contributed substantially to the common goal of this SFB for several reasons: First, project #05 had unique expertise and experience in the monitoring of TKI-treated patients with CML at the cytogenetic level (including FISH), molecular (MRD) level, and subclone-specific level. Project #05 had a unique collection of follow-up samples in CML and a close collaboration with clinical partners. Second, project #05 studied the evolution and expansion of BCR/ABL-mutant-bearing subclones in the context of additional (new) molecular lesions and lesion-patterns identified in other SFB project parts. Project #5 also extended subclone-related concepts to other (Ph-) MPN where follow-up and MRD parameters were less well established.
Based on experience in the CML model, studies in project #05 were expected to reveal similar ways and possibilities of monitoring, and finally explaining the basis of subclone evolution, expansion and depletion in JAK2 V617F+ MPN and KIT D816V+ SM/MCL. All in all, project #05 was an integral component of the SFB network.