2022 December 7

Gender plays a great role in the prognosis of Myelodysplastic Syndromes

An international team of researchers on Myelodysplastic Syndromes (MDS) has found that gender is an important factor in the progression of the disease with men showing a poorer prognosis mainly due to cardiovascular interactions of anemia with mild MDS and a worse and broader mutational landscape than women. The team proposes to incorporate sex and its associated distinctive features into the informed prognostic scoring system (IPSS), to better stratify MDS patients and improve personalized decision making in the clinic.

We know cancer makes no difference among people but that doesn't mean people react equally to cancer. The truth is there is a high heterogeneity among cancer patients, both on its progression and treatment response, and the first and most obvious difference is gender. Up until now, sex has been treated as a confounding factor in clinical trials, but recent evidence pointed out that it could have a strong prognostic power.

The Genomed4all consortium, an H2020 EU-funded initiative involving 23 institutions from 8 European countries, analyzed more that ten thousand samples from MDS patients to check whether including sex in their already calculated IPSS-R would make any difference. The IPSS-R is the international standard scoring system reflecting the severity of the disease for every patient and the main tool to decide on the treatment.

Dr. Francesc Sole, leader of the Myelodysplastic Syndromes Group at the Josep Carreras Leukaemia Research Institute, participated in the study that has been recently published in the top journal The Lancet Hematology. The reported results show that gender plays an important prognostic role, with males taking the worst part due to their increased susceptibility to cardiovascular disease, badly interacting with hematological disorders. Also, since men have only one X chromosome, are more prone to be affected by mutations with pathogenic impact on that chromosome than women.

On the other hand, women present an increased incidence of mutations in genes linked to poor prognosis, like TP53 and DNMT3A. However, their overall survival is better than men in all the studied cohorts.

As an outcome of the analysis, the Genomed4all consortium has developed a website to calculate a new prognostic scoring system including both gender and molecular information, that has allowed the re-stratification of roughly 40% of the patients in the cohorts. Re-stratification means a new perspective for the patient, more accurate to its individual condition and a more relevant and personalized treatment.

 

Reference article:

GenoMed4All consortium; “A sex-informed approach to improve the personalized decision-making process in myelodysplastic syndromes: a multicentre, observational cohort study”. The Lancet Hematology, https://doi.org/10.1016/S2352-3026(22)00323-4