Clinicopathologic Study of Isolated Del(20q) in De Novo Myelodysplastic Syndrome: A Group with Favorable Prognosis and No Evidence of Common Oncogenic Mutations.
Rashmi Kanagal Shamanna, Roberto N Miranda, C Cameron Yin, Carlos E Bueso-Ramos, Ramya Muddasani, L Jeffrey Medeiros, Gary Lu. UT MD Anderson Cancer Center, Houston, TX
Background: Del(20q) is a recurrent karyotypic abnormality that occurs in <5% of myelodysplastic syndromes (MDS). The WHO classification does not regard del(20q) as presumptive evidence of MDS in the absence of morphologic evidence of dysplasia. According to the International Prognostic Scoring System (IPSS) criteria for MDS, del(20q) as an isolated abnormality portends a relatively good prognosis, however, its association with oncogene mutations involving FLT3, RAS, KIT and NPM1 has not been evaluated.
Design: We searched for cases of de novo MDS with isolated del(20q) from the cytogenetics database. Therapy-related MDS cases with del(20q) were excluded. Clinicopathologic data were reviewed and Kaplan-Meier curve was used to estimate overall survival. DNA from bone marrow (BM) samples was amplified by polymerase chain reaction and evaluated for mutations in FLT3 and NMP1 (direct sequencing); RAS and KIT mutations (capillary electrophoresis).
Results: We identified 26 MDS cases with isolated del(20q). There were 22 men and 4 women, with a median age of 68 years (48-88). BM was hypercellular (median-60%, 25-95) with a median blast count of 2% (0-18). All cases had morphologic evidence of dysplasia, prominently in megakaryocytic (20/25) and erythroid (19/25) lineages. Granulocytic dysplasia was mild (15/25). Cases were classified using WHO 2008 classification as: refractory cytopenia with multilineage dysplasia (12/26), refractory anemia with excess blasts (6/26), refractory anemia (1/26), refractory anemia with ringed sideroblasts (2/32) and MDS-Unclassified (1/26). The median hemoglobin concentration was 10.9 g/dl (8.2-15.4), platelet count was 89x109/L (15-411) and median absolute neutrophil count was 1.61x109/L (0.1 – 3.95), with 12 transfusion dependent patients. IPSS scores included low (12/26), intermediate-1 (13/26) and intermediate-2 (1/26). The median overall survival was 64 months (26-99) with a median follow-up time of 81 months. 14 patients died (2/14 evolved into acute myeloid leukemia); 12 patients are alive with persistent disease. FLT3 (0/25), RAS (0/24), NPM1 (0/9), and KIT (0/12) mutations were absent in all cases.
Conclusions: De novo MDS with isolated del(20q) is a distinct category of MDS with a favorable prognosis. Although literature suggests that morphologic dysplasia is uncommon in this entity, all cases of MDS in this study had overt morphological dysplasia involving predominantly megakaryocytic and erythroid lineages. Oncogenic mutations involving FLT3, RAS, NPM-1 and KIT were not identified.
Monday, February 28, 2011 1:00 PM
Poster Session II # 170, Monday Afternoon