The iCMLf Genomics Alliance

In 2008 the iCMLf established a global CML Genomics Alliance to answer key clinical questions around the role of genetic mutations in clinical outcomes for CML. A literature review conducted by the iCMLf CML Genomics Alliance1, examined studies that reported mutated genes in adult patients with CML and established a clear, clinical need for further genomic evaluation in CML. Many clinical questions could be answered by pooling data. For example: Clinical relevance of mutations at diagnosis? Do some mutations confer a poorer prognosis? Can poor risk be overcome with more potent drugs? Will mutations at diagnosis impact the chance of treatment-free remission? CML is characterised by genomic aberration of the BCR-ABL1 gene, but other cancer gene mutations are detected at diagnosis and in advanced phases and may be more frequent than the BCR-ABL1 kinase domain mutations. The iCMLf Genomics Alliance research project aims to elucidate the hierarchy of genomic events that underlie the disease course in CML. Key research questions are to investigate if certain mutations might be associated with an increased risk in terms of TKI response and progression and how this knowledge could influence our therapeutic decision-making. The ultimate goal is to improve CML management and patient outcomes. To obtain insights into the role of mutations other than BCR-ABL1 kinase domain mutations, a large database with clinical and genetic data from thousands of patients is required.

Big data to improve CML treatment ‘The HARMONY Plus Big Data platform now provides the opportunity to move forward to answer multiple clinical questions in CML’ (Sue Branford) The HARMONY Big Data Project facilitates data pooling and sharing for specific hematologic malignancies with a central repository of data. Genomic and clinical data is collected from multiple research groups that contribute anonymized data in a secure way following all legal and ethical requirements. HARMONY Plus is an extension to the project to expand the scope of data sharing to other hematologic malignancies, including CML. The HARMONY Plus project team is collaborating with the iCMLf Genomic Alliance to facilitate the contribution of clinical and genetic CML data to HARMONY Plus to answer key clinical questions using Big Data.