The iCMLf Genomics Alliance - Investigating clonal hierarchy in CML

The iCMLf Genomics Alliance is now partnering with the HARMONY Big Data platform to analyse genetic data from thousands of CML patients. A novel iCMLf Genomics Alliance research project, led by Professor Thomas Ernst (University Hospital Jena, Germany) will study the role of genetic aberrations in the disease course of CML.

'A goal of the iCMLf Genomics Alliance is to pool mutatational data through a shared database. This will enhance statistical power in order to understand the impact of genomic variation on treatment response for patients with CML' (Sue Branford – Chair of the iCMLf Genomics Alliance)

The iCMLf is leading the way to bring the CML community together to contribute genomic and clinical data to the HARMONY Plus database and use ‘Big Data’ to answer key questions in CML. The first project aims to elucidate the hierarchy of genomic events that underlie the disease course in CML. Currently, we have enrolled 13 sites from 11 countries, with expectations of including over 1,400 cases.

We welcome further interest from groups to contribute data, or ideas for future analysis.

History of the iCMLf/HARMONY research project to investigate clonal hierarchy in CML

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.

HARMONY Plus platform – 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.

iCMLf invites the CML community to contribute data

The iCMLf encourages partners and other interested parties to participate in the project, to define variables for data collation and to commence the submission of datasets to HARMONY Plus.

If you are interested to contribute data or ideas to HARMONY Plus, please email info@cml-foundation.org.

Make a difference in the fight against CML

You can donate to the iCMLf research projects by visiting our donation page to get involved and make a difference in the fight against CML.

We are grateful to Pfizer and Incyte for support for the analysis and publication of the iCMLf Alliance projects.

(1) Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia. Branford S et al. Leukemia 2019:33:1835