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Blood, 22 October 2009, Vol. 114, No. 17, pp. 3538-3545. Prepublished online as a Blood First Edition Paper on August 19, 2009; DOI 10.1182/blood-2009-05-222331. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-05-222331v1 114/17/3538    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Malcovati, L. Articles by Cazzola, M. PubMed PubMed Citation Articles by Malcovati, L. Articles by Cazzola, M. Related Collections Free Research Articles Myeloid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis Luca Malcovati1, Matteo G. Della Porta1, Daniela Pietra1, Emanuela Boveri2, Andrea Pellagatti3, Anna Gallì1, Erica Travaglino4, Angela Brisci5, Elisa Rumi1, Francesco Passamonti1, Rosangela Invernizzi4, Laura Cremonesi5, Jacqueline Boultwood3, James S. Wainscoat3, Eva Hellström-Lindberg6, and Mario Cazzola1 Departments of 1 Hematology Oncology and 2 Human Pathology, University of Pavia & Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; 3 Leukaemia Research Fund Molecular Haematology Unit, John Radcliffe Hospital, Oxford, United Kingdom; 4 Department of Medicine, University of Pavia & Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 5 Genomic Unit for the Diagnosis of Human Pathologies, San Raffaele Scientific Institute, Milan, Italy; and 6 Department of Medicine, Division of Hematology, Karolinska Institutet, Stockholm, Sweden 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 109/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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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