Cytogenetics is an important predictor of survival in patients with myeloid malignancies including myelodysplastic syndromes (MDS). The roles of balanced chromosomal rearrangements (BCR) specifically balanced translocations and inversions in MDS are less established. We hypothesized that BCR are commonly found in MDS and might confer important prognostic and therapeutic effect.
PATIENTS AND METHODS:
Cytogenetic, hematologic, clinical, and survival data from a total of 302 MDS patients seen at the Cleveland Clinic between the years 2002 and 2011 were collected. Direct sequencing for genes relevant in MDS pathophysiology was performed on patients with BCR. Categorical data were analyzed using the χ2 test and survival outcomes were analyzed using the Kaplan-Meier method.
Twenty-three patients (8%) carried non-t(6;9) and non-inv(3) BCR. These patients had short overall survival (OS) similar to patients with poor risk cytogenetics, defined according to the International Prognostic Scoring System, which was not altered by new single-nucleotide polymorphism arrays or acquired somatic uniparental disomy lesions. Among the detected somatic mutations, only patients harboring mutations in the RNA splicing gene serine/arginine-rich splicing factor 2 (SRSF2) conferred worse outcomes in this group of patients. Therapeutically, patients who received allogeneic hematopoietic cell transplantations had better OS compared with patients treated with pharmacologic therapies or best supportive care only.
BCR are not common in MDS and are associated with poor survival, which might be influenced by the presence of SRSF2 mutation.