Absence of a common founder mutation in patients with cooccurring myelodysplastic syndrome and plasma cell disorder

Abstract

Epidemiological studies have demonstrated an increased incidence of MDS in patients with plasma cell disorder (PCD) i.e. multiple myeloma (MM) or MGUS and several case reports / series of co-occurring MDS and PCD have been published. The underlying pathogenesis for this condition, and if the two diseases share a common genetic lesion remains unknown. Here, we describe a cohort of 27 consecutive patients with co-occurring MDS and MM (n=6), MGUS (n=20) or plasmocytoma (n=1), diagnosed at the Karolinska University Hospital. In 5 patients, the diagnosis of MGUS preceded the diagnosis of MDS , in one patient the MDS diagnosis preceded PCD, and in 21 patients MDS and PCD were diagnosed at the same time. There was a preponderance for lower-risk MDS subgroups with only 3 patients belonging to the IPSS-R high / very high risk groups. Median overall survival for the whole cohort was 44 months. The most common mutations were TET2, SRSF2 and SF3B1. To identify potential common founder clones, we performed whole exome sequencing on isolated bone marrow myeloid-, plasma- and T-cells from 9 patients. In none of the patients, we could detect a common founder mutation and the two diseases have likely emerged from separate clones.