Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation

Abstract

JAK2 V617F mutation recently was identified as a pathogenic factor in typical chronic myeloproliferative diseases (CMPD). Some forms of myelodysplastic syndromes (MDS) show a significant overlap with CMPD (classified as MDS/MPD), but the diagnostic assignment may be challenging. We studied blood or bone marrow from 270 patients with MDS, MDS/MPD, and CMPD for the presence of JAK2 V617F mutation using polymerase chain reaction, sequencing, and melting curve analysis. The detection rate of JAK2 V617F mutants for polycythemia vera, chronic idiopathic myelofibrosis, and essential thrombocythemia (n ‫؍‬ 103) was similar to the previously reported results. In typical forms of MDS (n ‫؍‬ 89) JAK2 V617F mutation was very rare (n ‫؍‬ 2). However, a higher prevalence of this mutation was found in patients with MDS/MPD-U (9 of 35). Within this group, most of the patients harboring JAK2 V617F mutation showed features consistent with the provisional MDS/MPD-U entity refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T). Among 9 RARS-T patients, 6 showed the presence of JAK2 V617F mutation, and in 1 patient without mutation, aberrant, positive phospho-STAT5 staining was seen that is typically present in association with JAK2 V617F mutation. In summary, we found that RARS-T reveals a high frequency of JAK2 V617F mutation and likely constitutes another JAK2 mutation-associated form of

Mutations of JAK2 and TET2, but not CBL are detectable in a high portion of patients with refractory anemia with ring sideroblasts and thrombocytosis

“…1 These light chains do not fold into the proper tertiary conformation and form protein deposits, causing organ damage. 2 The most commonly affected organs are the heart, liver, kidney, gut, and peripheral nerves. 3 Standard treatment for patients with good performance status includes highdose melphalan with autologous stem cell transplantation (ASCT).…”

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…Moreover, refractory anemia with ring sideroblasts (RARS-T) and thrombocytosis has to be considered, because of the problematic distinction between this overlap syndrome and MPN, particularly, when myelodysplastic features are not very conspicuous [42,43]. On the other hand, ring sideroblasts are not an uncommon finding in MPN and the recent demonstration of a relatively high frequency for JAK2V617F and MPL mutations [44][45][46][47][48][49][50][51][52][53] confirms previous clinicopathological studies about the heterogeneity of this disorder [54]. These data support the persistent discussion about the relationship of these cases with true MPN [49] including prodromal stages, but especially prefibrotic PMF according to the WHO classification [54] without markedly expressed myelodysplasia.…”

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

“…Chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical BCR-ABL1-negative chronic myeloid leukemia, MDS/MPN unclassifiable, refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) are included (19). The patient in the present case was carrier of a JAK2 (V617F) mutation, which is more common in ET compared with MDS patients (3,16,(19)(20)(21)(22). The JAK2 (V617F) mutation is described in >95% of polycythemia vera and 50-60% of ET and myelofibrosis patients.…”