Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis

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

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Abstract

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.

Original languageEnglish
Pages (from-to)3538-3545
Number of pages8
JournalBlood
Volume114
Issue number17
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Malcovati, L., Della Porta, M. G., Pietra, D., Boveri, E., Pellagatti, A., Gallì, A., Travaglino, E., Brisci, A., Rumi, E., Passamonti, F., Invernizzi, R., Cremonesi, L., Boultwood, J., Wainscoat, J. S., Hellström-Lindberg, E., & Cazzola, M. (2009). Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood, 114(17), 3538-3545. https://doi.org/10.1182/blood-2009-05-222331