Characterization of Clonal Abnormalities in Refractory Anemia with Ringed Sideroblasts and Associated Thrombocytosis (RARS-T).
Jitakshi De. Genoptix Medical Laboratory, Carlsbad, CA
Background: Refractory anemia with ringed sideroblasts and associated thrombocytosis (RARS-T) is a rare clonal hematopoietic neoplasm within the spectrum of a low grade MDS and MPN. Though RARS-T has a known association with JAK2 V617F mutation, and rarely MPL W515 K/L mutation, the frequency of these mutations and their relation with the platelet count and acquired cytogenetic abnormalities has not been studied in a large series of cases.
Design: A database search was performed for cases diagnosed between Jan '07 to Sep '10 with RARS-T and had a platelet count (PLT) >400 K/ul. Only cases in which cytogenetics and JAK2 V617F mutation analysis were performed by qRT-PCR were included. The 26 cases, including 3 that had a subsequent follow-up evaluation after 11-39 months, were retrospectively reviewed.
Results: The age range was 62 – 94 years, with a male to female ratio of 1.6:1. The average CBC at presentation was WBC: 7.8 K/ul (4.2-12.1 K/ul), Hb: 10.0 g/dL (6.9-14.1), MCV: 97.5 fL (86.7-112.7), and PLT: 644 K/ul (422 – >1000). The median PLT was 575 K/ul. Morphology and flow cytometry showed no increase in blasts. JAK2 mutation was identified at low levels (1-20% mutant transcript) in 12/26 cases (46%) and in all 6 cases with PLT >800K/ul, in 6/12 (50%) with PLT of 450-800K/ul, and in 0/3 cases with PLT of 400-450 K/ul (p=0.007). None of the 13 cases in which the analysis was performed was positive for MPL W515K/L mutation. Cytogenetic abnormalities were found in 8/26 cases (31%). The most common abnormality was +8 which was found in 3/26 cases (11.5%), of which one had an additional abnormality of del (1p12), and it was JAK2-negative. One case each had del (17q), t(1;3)(p22;p22), del (13q), del (20q), and –Y, respectively. There was no correlation between cytogenetic abnormalities and the presence of JAK2 V617F mutation. In 2/3 cases that had a follow-up evaluation, PLT increased slightly and in the third case it decreased, but remained >450 K/ul. None of these 3 cases showed an increase in blasts or had additional cytogenetic abnormalities at follow-up.
Conclusions: RARS-T is a heterogeneous disorder with low level JAK2 mutation detectable in ∼ half of the cases. MPL mutations are extremely rare, and not found in this series. Trisomy 8 is the most common chromosomal abnormality. A clonal abnormality is undetectable in a significant proportion of cases. JAK2-positivity correlates with the platelet count, with >800K/ul significantly more likely to have a JAK2 mutation. Additional studies are necessary to further characterize this unusual entity.
Monday, February 28, 2011 1:00 PM
Poster Session II # 174, Monday Afternoon