logo logo
Search: Organ site Search: Tumor / Syndrome
or
WHO Classification of Tumours
Refractory anaemia with ring sideroblasts associated with marked thrombocytosis
Tumours of haematopoietic and lymphoid tissues


Definition

In the third edition of the WHO Classification, RARS-T, previously also referred to as essential thrombocythaemia (ET) with ring sideroblasts, was proposed as a provisional entity to encompass patients who have the clinical and morphological features of the myelodysplastic syndrome, RARS, but who also have marked thrombocytosis associated with abnormal megakaryocytes similar to those observed in the BCR-ABL1-negative MPN, such as ET or early-stage primary myelofibrosis (PMF)
Click to access Pubmed
Gupta R, Abdalla SH, Bain BJ (1999)
Thrombocytosis with sideroblastic erythropoiesis: a mixed myeloproliferative myelodysplastic syndrome.
Leuk Lymphoma 34: 615-9




Click to access Pubmed
Juneja SK, Imbert M, Jouault H, Scoazec JY, Sigaux F, Sultan C (1983)
Haematological features of primary myelodysplastic syndromes (PMDS) at initial presentation: a study of 118 cases.
J Clin Pathol 36: 1129-35




Click to access Pubmed
Streeter RR, Presant CA, Reinhard E (1977)
Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia.
Blood 50: 427-32



. However, some investigators have suggested that RARS-T is not a unique entity but instead represents cases of other subtypes of MDS or well-defined MPN that have acquired ring sideroblasts as a secondary form of dysplasia
Click to access Pubmed
Schmitt C, Balogh B, Grundt A, Buchholtz C, Leo A, Benner A, Hensel M, Ho AD, Leo E (2006)
The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, breakpoints, and detection method validity.
Leuk Res 30: 745-50



. It is not clear whether RARS-T is a distinct entity, one end of the spectrum of RARS, a progression of RARS due to an additional acquired genetic abnormality, or less likely, the occurrence of two rare diseases in the same patient. Therefore, until these questions are more clearly answered, RARS-T remains a provisional entity.

In support of a myeloproliferative component to this neoplasm, the majority of cases reported as RARS-T have shown the JAK2 V617F mutation, or much less commonly, the MPL W515K/L mutation

Click to access Pubmed
Boissinot M, Garand R, Hamidou M, Hermouet S (2006)
The JAK2-V617F mutation and essential thrombocythemia features in a subset of patients with refractory anemia with ring sideroblasts (RARS).
Blood 108: 1781-2




Click to access Pubmed
Ceesay MM, Lea NC, Ingram W, Westwood NB, Gäken J, Mohamedali A, Cervera J, Germing U, Gattermann N, Giagounidis A, Garcia-Casado Z, Sanz G, Mufti GJ (2006)
The JAK2 V617F mutation is rare in RARS but common in RARS-T.
Leukemia 20: 2060-1




Click to access Pubmed
Gattermann N, Billiet J, Kronenwett R, Zipperer E, Germing U, Nollet F, Criel A, Selleslag D (2007)
High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count>600x109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable.
Blood 109: 1334-5




Click to access Pubmed
Remacha AF, Nomdedéu JF, Puget G, Estivill C, Sarda MP, Canals C, Aventin A (2006)
Occurrence of the JAK2 V617F mutation in the WHO provisional entity: myelodysplastic/myeloproliferative disease, unclassifiable-refractory anemia with ringed sideroblasts associated with marked thrombocytosis.
Haematologica 91: 719-20




Click to access Pubmed
Renneville A, Quesnel B, Charpentier A, Terriou L, Crinquette A, Laï JL, Cossement C, Lionne-Huyghe P, Rose C, Bauters F, Preudhomme C (2006)
High occurrence of JAK2 V617 mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis.
Leukemia 20: 2067-70




Click to access Pubmed
Schnittger S, Bacher U, Haferlach C, Dengler R, Kröber A, Kern W, Haferlach T (2008)
Detection of an MPLW515 mutation in a case with features of both essential thrombocythemia and refractory anemia with ringed sideroblasts and thrombocytosis.
Leukemia 22: 453-5




Click to access Pubmed
Steensma DP, Caudill JS, Pardanani A, McClure RF, Lasho TL, Tefferi A (2006)
MPL W515 and JAK2 V617 mutation analysis in patients with refractory anemia with ringed sideroblasts and an elevated platelet count.
Haematologica 91: ECR57




Click to access Pubmed
Szpurka H, Tiu R, Murugesan G, Aboudola S, Hsi ED, Theil KS, Sekeres MA, Maciejewski JP (2006)
Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation.
Blood 108: 2173-81




Click to access Pubmed
Wang SA, Hasserjian RP, Loew JM, Sechman EV, Jones D, Hao S, Liu Q, Zhao W, Mehdi M, Galili N, Woda B, Raza A (2006)
Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features.
Leukemia 20: 1641-4



. On the other hand, the few reported cases with this mutation that have been studied for endogenous colony formation in vitro have demonstrated a pattern more akin to that of MDS
Click to access Pubmed
Boissinot M, Garand R, Hamidou M, Hermouet S (2006)
The JAK2-V617F mutation and essential thrombocythemia features in a subset of patients with refractory anemia with ring sideroblasts (RARS).
Blood 108: 1781-2




Click to access Pubmed
Remacha AF, Nomdedéu JF, Puget G, Estivill C, Sarda MP, Canals C, Aventin A (2006)
Occurrence of the JAK2 V617F mutation in the WHO provisional entity: myelodysplastic/myeloproliferative disease, unclassifiable-refractory anemia with ringed sideroblasts associated with marked thrombocytosis.
Haematologica 91: 719-20



. Thus it may be that the provisional designation of an MDS/MPN accurately reflects the underlying biology in a substantial proportion of the patients
Click to access Pubmed
Gattermann N, Billiet J, Kronenwett R, Zipperer E, Germing U, Nollet F, Criel A, Selleslag D (2007)
High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count>600x109/L) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable.
Blood 109: 1334-5



; more study is needed to further clarify this disorder.
Cases of MDS associated with isolated del(5q) and of AML with inv(3)(q21q26.2)or t(3;3)(q21;q26.2);RPN1-EVI1 are excluded from this category, as are cases with a BCR-ABL1 fusion gene. In addition, if there has been a prior diagnosis of an MPN without ring sideroblasts, or there is evidence that the ring sideroblasts might be a consequence of therapy or represent disease progression in a patient with features that meet the criteria of another well-defined MPN, this designation should not be used.

> Related Topics
Essential thrombocythemia
Refractory anemia with ring sideroblasts
Myelodysplastic syndrome associated with isolated del(5q)
Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Introduction: Myeloid Neoplasms