2018 October 23

An update on research into MDS at our centre

Research into myelodysplastic syndromes at the Josep Carreras Leukaemia Research Institute (IJC) is bearing fruit as the research group into this disease publishes its fifth new scientific article this year.  We talked to Francesc Solé, Scientific Director of IJC Campus ICO-GTP (Badalona) and MDS Group Leader to ask about the group’s work.

MDS is a very complex disease, with different patients showing different alterations in their chromosomes, but you seem to be tackling many different questions here.

FS: Well, of course the more we find out, the more complexity we uncover, but the objective here is to understand how these alternations will affect whether a person  will develop symptoms, and in the case of those who have MDS, whether it will transform to acute myeloid leukemia (AML).  The more accurately we can diagnose people, the better their doctor can treat them, and if necessary check other members of the family.

You have identified a difference in variations in the genes SAMD9 and SAMD9L in adults and children recently in a paper published in the journal Blood.

FS: Yes, in this collaboration with Japanese, Swedish, American and Spanish scientists we looked at these two genes.   Children who inherit a faulty gene from a parent tend to develop bone marrow failure at an early age, whereas adult patients with MDS have probably not inherited the fault but have acquired it later, then with the accumulation of other alterations they had developed MDS. In fact we found that although the same gene was affected, we were looking at different changes in adults and children.  Although it is a very small group of adults with this change, the effects are not the same as other alterations that cause MDS and they must be treated accordingly.

Another paper in the journal Genes Chromosomes and Cancer looks at patients with more than one alteration in their genes.

FS: Indeed, this is another important factor.  Patients all over the world are diagnosed by looking at their chromosomes (cytogenetics) and classifying them according to one of the international systems (International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) or the NCCSS sytem developed in 2012.  We looked at this last one.  As patients can have groups of cells in their blood with the same genetic make up (clones) it has been known for a long time that the NCCSS system does not take into account whether multiple abnormalities are occurring in just one or more than one clone in the same patient.  This paper describes how it is better to calculate the number of abnormalities in the complete sample and not just per clone, for patients with multiple alterations. This makes for a more accurate prognosis and calculation of the risk of them developing AML.

We earlier reported a study into MDS patients, where you found that whether patients came from Japanes or caucasian backgrounds affected how their disease might develop  these are all very international studies.

FS. Absolutely, in today’s research we do not just look at small numbers of patients in a local area.  We access data from patients from international databases and can study samples stored in the same conditions in different biobanks all over the world.  Using powerful statistical calculations we can tease out differences that may affect only a very few patients, but that it would be impossible to find by only looking at their samples alone.  We are able to extract information from the data and pass this back to the doctors so they can tailor their treatment to each patient. 

This is personalized medicine?

FS: Yes, it is, and we are improving, but we still have a long way to go.  For this  reason the IJC is contributing with its sample collection.  We are collecting samples and data from patients who give their consent to participate in research and this data is contributing to the international databases and projects mentioned.

And not only the scientists and patients are international ...

FS: No, the funding is international too; our own group receives funding from the Spanish Government from the Instituto Carlos III and the Ministry of Economy and Competitiveness (PI/14/00013; PI/ 17/0575), the Government of Catalonia, the Generalitat (2017 SGR288, GRC and the CERCA institute); the International Josep Carreras Foundation and Celgene.  Development of our discoveries is supported by the ʺla Caixa“ Foundation and the company Celgene. Obviously all our collaborators on these studies have their own lists. 

Modern research is a team effort then?

FS: It is, with all the administration that goes wth coordinating large international groups of people! Scientists work in large networks of experts with different people contributing different expertise to each study.  Laboratories across the world are sharing samples, data, techniques and know-how,all with the objective of helping individual patients who are talking to their doctor about their MDS diagnosis.  It is the thought of these individuals that keeps us all working hard looking for more answers.



Original papers

Nagata et al, Germline SAMD9 and SAMD9L alterations in adult myelodysplastic syndrome. Blood.  PMID:   30322869. IF:  13.164.

Schanz J et al Clonal architecture in patients with myelodysplastic syndromes and double or minor complex abnormalities: Detailed analysis of clonal composition, involved abnormalities, and prognostic significance.  Genes Chromosomes Cancer 24 Sep 2018, . Epub 24 Sep 2018

All the groups publications this year