Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status

Abstract

The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.

Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis

“…Raya et al have already answered this question in a previous study in which they show that there was no difference in survival between the two groups. 15 Our study confirmed this finding in a large series since no difference was noted in the outcome according to the platelet threshold.…”

“…15,18 Our results clearly show that no difference was observed in the survival rate between JAK2V617F positive and negative RARS-T patients.…”

“…Julien Broseus, 1 Lourdes Florensa, 2 Esther Zipperer, 3 Susanne Schnittger, 4 Luca Malcovati, 5 Steven Richebourg, 6 Eric Lippert, 7 Jaroslav Cermak, 8 Jyoti Evans, 9 Morgane Mounier, 10 José Maria Raya, 11 François Bailly, 1 Norbert Gattermann,3 Torsten Haferlach, 4 Richard Garand, 6 Kaoutar Allou, 7 Carlos Besses, 12 Ulrich Germing, 3 Claudia Haferlach, 4 Erica Travaglino, 5 Elisa Luno, 13 Maria Angeles Pinan, 14 Leonor Arenillas, 2 Maria Rozman, 15 Maria Luz Perez Sirvent, 16 Bernardine Favre, 1 Julien Guy, 1 Esther Alonso, 18 Nuhri Ahwij, 19 Andrés Jerez, 20 Sylvie Hermouet, 17 Marc Maynadié, 1,10 Mario Cazzola, 5 and François Girodon …”

“…6 In particular, their presence in the bone marrow (15% or more) is a marker of the myelodysplastic syndrome defined as RARS which is characterized by both morphological dysplasia in only the erythroid lineage and a favorable clinical outcome. 7,8 Mutations in the Janus Kinase 2 gene (JAK2) and/or myeloproliferative leukemia protein gene (MPL) have been detected in 50-60% of patients with RARS-T. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] Some of us recently showed that RARS-T is indeed a myeloid neoplasm with both myelodysplastic and myeloproliferative features at the molecular and clinical level, and that it may develop from RARS through the acquisition of somatic mutations of JAK2, MPL or other as yet unknown genes. 14 This conclusion was recently confirmed by an independent observation.…”

The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

“…52 These findings have prompted some authorities to suggest that RARS-T should be moved to the MPN category, whereas others argued that RARS-T is not a distinct entity at all, but rather an MPN that has undergone genetic For personal use only. on May 9, 2018. by guest www.bloodjournal.org From evolution to acquire ring sideroblasts.…”