Refractory anemia with ring sideroblasts and RARS with thrombocytosis

Abstract

Disease Overview: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS‐T). Diagnosis: RARS is a lower risk myelodysplastic syndrome (MDS) with dysplasia limited to the erythroid lineage, <5% bone marrow (BM) blasts and ≥15% BM RS. RARS‐T is a provisional entity in the MDS/MPN (myeloproliferative neoplasm) overlap syndromes, with diagnostic features of RARS, along with a platelet count ≥450 × 10(9)/L and large atypical megakaryocytes similar to those observed in BCR‐ABL1 negative MPN. Mutations and Karyotype: Mutations in the SF3B1 gene are seen in ≥80% of patients with RARS and RARS‐T, and strongly correlate with the presence of BM RS; RARS‐T patients have additional mutations such as, JAK2V617F (∼60%), MPL (<5%), and CALR (<5%). Cytogenetic abnormalities are uncommon in both RARS and RARS‐T. Risk stratification: Most patients with RARS are stratified into lower risk groups by the International Prognostic Scoring System (IPSS) for MDS and the revised IPSS. Disease outcome in RARS‐T is better than that of RARS, but worse than that of essential thrombocytosis. Both RARS and RARS‐T have a low risk of leukemic transformation. Treatment: Anemia and iron overload are complications in both diseases and are managed similar to lower risk MDS. Aspirin therapy is reasonable in RARS‐T, especially in the presence of JAK2V617F, but the value of platelet‐lowering drugs is uncertain. Case reports of RARS‐T therapy with lenalidomide warrant additional studies. Am. J. Hematol. 90:550–559, 2015. © 2015 Wiley Periodicals, Inc.

Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) and the role of next‐generation sequencing

“…It is believed that MPN-like features in RARS-T are driven by MPN-like mutations such as, JAK2V617F [2]. In the current study, 33% of patients had a JAK2 mutation detected by NGS, while 42% were positive by the more sensitive allele specific PCR assay.…”

“…Based on the 2008 WHO criteria, RARS-T is considered a provisional entity in the MDS/MPN overlap syndrome category [1,2]. While it is important to distinguish RARS-T from ET with BM RS and RARS with reactive thrombocytosis, this distinction is often difficult based on morphology alone.…”

“…The detection of bone marrow (BM) RS can be seen in a variety of clonal hematological and non-clonal disorders [2]. Myeloid neoplasms characterized by the presence of BM RS include refractory anemia with ring sideroblasts (RARS), and RARS with thrombocytosis (RARS-T), a provisional entity included in MDS/MPN (myelodysplastic syndromes/myeloproliferative neoplasms) overlap syndromes [1,2].…”

Myelodysplastic syndrome without ring sideroblasts and with Janus kinase 2 gene mutation: An unusual case report

“…The JAK2 (V617F) mutation is described in >95% of polycythemia vera and 50-60% of ET and myelofibrosis patients. However, in MDS, the JAK2 (V617F) mutation is found mainly in patients with RARS-T (refractory anemia with ring sideroblasts), which was excluded by Perls' staining (23)(24)(25). The histopathological and immunophenotypic studies as well as the presence of micromegakaryocytes and ALIP favored the diagnosis of MDS.…”

An update on BCR-ABL1-negative myeloproliferative neoplasms

“…The differential diagnosis in MPN includes other members of this category, the related refractory anaemia with ring sideroblasts with thrombocytosis (RARS-T) 6 and also entities such as MPN/MDS and MDS with isolated del(5q), which may present with thrombocytosis. 7 A variety of reactive disorders must be actively excluded before a diagnosis of MPN or MDS/MPN can be established.…”