Document Detail

Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis.
MedLine Citation:
PMID:  19692701     Owner:  NLM     Status:  MEDLINE    
We studied patients with myeloid neoplasm associated with ringed sideroblasts and/or thrombocytosis. The combination of ringed sideroblasts 15% or greater and platelet count of 450 x 10(9)/L or greater was found in 19 subjects fulfilling the diagnostic criteria for refractory anemia with ringed sideroblasts (RARS) associated with marked thrombocytosis (RARS-T), and in 3 patients with primary myelofibrosis. JAK2 and MPL mutations were detected in circulating granulocytes and bone marrow CD34+ cells, but not in T lymphocytes, from 11 of 19 patients with RARS-T. Three patients with RARS, who initially had low to normal platelet counts, progressed to RARS-T, and 2 of them acquired JAK2 (V617F) at this time. In female patients with RARS-T, granulocytes carrying JAK2 (V617F) represented only a fraction of clonal granulocytes as determined by X-chromosome inactivation patterns. RARS and RARS-T patient groups both consistently showed up-regulation of ALAS2 and down-regulation of ABCB7 in CD34+ cells, but several other genes were differentially expressed, including PSIP1 (LEDGF), CXCR4, and CDC2L5. These observations suggest that RARS-T is indeed a myeloid neoplasm with both myelodysplastic and myeloproliferative features at the molecular and clinical levels and that it may develop from RARS through the acquisition of somatic mutations of JAK2, MPL, or other as-yet-unknown genes.
Luca Malcovati; Matteo G Della Porta; Daniela Pietra; Emanuela Boveri; Andrea Pellagatti; Anna Gallì; Erica Travaglino; Angela Brisci; Elisa Rumi; Francesco Passamonti; Rosangela Invernizzi; Laura Cremonesi; Jacqueline Boultwood; James S Wainscoat; Eva Hellström-Lindberg; Mario Cazzola
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-19
Journal Detail:
Title:  Blood     Volume:  114     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-23     Completed Date:  2009-11-17     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3538-45     Citation Subset:  AIM; IM    
Department of Hematology Oncology, University of Pavia & Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Policlinico San Matteo, Pavia, Italy.
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MeSH Terms
Aged, 80 and over
Anemia, Refractory, with Excess of Blasts / genetics*,  pathology*
Bone Marrow / metabolism,  pathology
Cells, Cultured
Flow Cytometry
Gene Expression Profiling
Granulocytes / metabolism,  pathology
Janus Kinase 2 / genetics
Middle Aged
Mutation / genetics
Oligonucleotide Array Sequence Analysis
Platelet Count
Receptors, Thrombopoietin / genetics
T-Lymphocytes / metabolism,  pathology
Thrombocytosis / genetics*,  pathology*
Tumor Markers, Biological / genetics
X Chromosome Inactivation / genetics
Reg. No./Substance:
0/Receptors, Thrombopoietin; 0/Tumor Markers, Biological; 143641-95-6/MPL protein, human; EC Kinase 2; EC protein, human

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