Since 2016, inherited forms of myeloid malignancies, including MDS, have been included as a separate disease entity in the World Health Organisation (WHO) classification of haematological cancers.
This is leading to a greater awareness on behalf of haematologists regarding the existence of these forms of disease, enabling more tailored management of this group of at-risk individuals.
This is important, as patients with ‘familial MDS’ (i.e. with a predisposing mutation present in every cell) tend to develop symptoms at a much younger age compared to people with ‘sporadic disease’ (i.e. mutations are restricted to the MDS only).
We also appreciate that MDS can arise as part of a wider syndrome, with many patients/families initially exhibiting bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, and Shwachman–Diamond syndrome which often subsequently lead to MDS.
Why is it important to identify patients with familial MDS?
Our research is demonstrating that there isn’t a singly mutated gene responsible for familial MDS but many different genes,
some of which are also mutated in sporadic forms of the disease (RUNX1, GATA2). In comparison other mutations (in the germline) appear enriched or exclusive to inherited forms of MDS (DDX41, SAMD9) and this is offering researchers novel insights into the causes of MDS and the prospect of developing better treatments for all MDS patients.
It is, therefore, important that, when a new patient is diagnosed with MDS in the clinic, steps are taken to determine whether the disease has a significant genetic-inherited component. This is crucial, as in some subtypes of inherited/familial MDS subsequent therapy must be modified.
- For example, if a patient has MDS associated with an underlying telomerase mutation then the chemotherapy conditioning regimen performed prior to a bone marrow transplant has to be reduced.
- Equally, a haematologist would want to ensure that, in selecting bone marrow/stem cell donors, an asymptomatic family member with the same genetic defect is not used as the donor as the recipient could go on to develop MDS again at a later time point./li>