Genetic mutation signifies new MDS subtype

Published in Blood, a special report has proposed a new, distinct subtype of myelodysplastic syndromes (MDS) based on the presence of somatic mutation; SF3B1. Half of MDS patients carry somatic mutations in spliceosome genes; SF3B1 is the most commonly mutated, with a prevalence of around 20%.1

“This study represents an important step forward in the ability to diagnose MDS on the basis of genetic features, and this is paving the way to obtain a diagnosis without the need to analyze bone marrow,” said lead author Luca Malcovati, MD, of the University of Pavia Medical School, Italy.

Patients who carry this genetic variant may benefit from treatment with an approved drug, luspatercept. In addition, other potential new treatments that directly target this genetic mutation are in the early stages of development and may benefit patients in the future.”2

Patients with MDS who carry this genetic variant tend to have a less severe or aggressive form of the disease. Additionally, a recent trial demonstrated high response rates in patient populations with the SF3B1 mutation treated with luspatercept.3

Luspatercept was approved by the U.S. Food and Drug Administration (FDA) in November 2019 for the treatment of anemia in MDS patients. In this video, filmed at the 2020 MDS meeting held in Tel Aviv, Alan List, MD, discusses the mechanisms of luspatercept as well as the trial data supporting its use in patients with MDS.

SF3B1-mutated MDS tends to be associated with ring sideroblast red blood cells (RBCs) that result from the impact of the mutation on RBCs utilization of iron. The resulting impairment in hemoglobin production leads to the characteristic anemia associated with SF3B1-mutated MDS.2

The researchers concluded that SF3B1-mutated MDS has three main distinctive features: ineffective erythropoiesis, a relatively good prognosis, and favorable prospects when anemia is treated with luspatercept, which encourages the growth and expansion of RBCs.1

The identification of this distinct subtype of MDS bodes well for the research directions and patient stratification of a disease area that is now really starting to pick up speed.

Written by Thomas Southgate


1)    Malcovati L, Stevenson K, Papaemmanuil E et al. SF3B1-mutant myelodysplastic syndrome as a distinct disease subtype – A Proposal of the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM). Blood. April 2020; doi: 10.1182/blood.2020004850. [Epub ahead of print].
2) New MDS Subtype Proposed Based on Presence of Genetic Mutation. Available from: (Last accessed: 01/05/2020).
3)    Fenaux P, Platzbecker U, Mufti GJ et al. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. ­New England Journal of Medicine. 2020 Jan 9;382(2):140-151.