and RARS-T so far, it had not been possible to define significant differences in the clinical outcome based on the MPLW515 mutational status. 8 Only molecular screening of a larger number of cases of CMPD also mimicking features of RARS-T for MPLW515 mutations will reveal the frequency in these borderline cases. It further remains to be clarified whether JAK2 and MPL mutations can occur in coincidence in RARS-T as it was occasionally reported in CIMF. 7 The different phenotypes of MPLW515-associated disordersFET, CIMF and RARS-TFem- phasize that these disorders are probably the result of a more complex genetic network that remains to be clarified by further analysis of positive and negative regulators of the JAK–STAT pathway. 8 S Schnittger 1 , U Bacher 2 , C Haferlach 1 , R Dengler 3 , A Kro ¨ber 3 , W Kern 1 and T Haferlach 1 1 MLLFMunich Leukemia Laboratory, Munich, Germany; 2 Stem Cell Transplantation, University Hospital of Hamburg- Eppendorf, Hamburg, Germany and 3 Ha ¨matologisch-Onkologische Praxis, Regensburg, Germany E-mail: Susanne.Schnittger@mll-online.com References 1 Szpurka H, Tiu R, Murugesan G, Aboudola S, Hsi ED, Theil KS et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood 2006; 108: 2173–2181. 2 Boissinot M, Garand R, Hamidou M, Hermouet S. The JAK2-V617F mutation and essential thrombocythemia features in a subset of patients with refractory anemia with ring sideroblasts (RARS). Blood 2006; 108: 1781–1782. 3 Ceesay MM, Lea NC, Ingram W, Westwood NB, Gaken J, Mohamedali A et al. The JAK2 V617F mutation is rare in RARS but common in RARS-T. Leukemia 2006; 20: 2060–2061. 4 Gattermann N, Billiet J, Kronenwett R, Zipperer E, Germing U, Nollet F et al. High frequency of the JAK2 V617F mutation in patients with thrombocytosis (platelet count4600  10 9 /l) and ringed sideroblasts more than 15% considered as MDS/MPD, unclassifiable. Blood 2007; 109: 1334–1335. 5 Shaw GR. Ringed sideroblasts with thrombocytosis: an uncommon mixed myelodysplastic/myeloproliferative disease of older adults. Br J Haematol 2005; 131: 180–184. 6 Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both ‘atypical’ myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106: 1207–1209. 7 Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472–3476. 8 Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270. 9 Schnittger S, Bacher U, Kern W, Schroder M, Haferlach T, Schoch C. Report on two novel nucleotide exchanges in the JAK2 pseudokinase domain: D620E and E627E. Leukemia 2006; 20: 2195–2197. The DC-derived protein DC-STAMP influences differentiation of myeloid cells Leukemia (2008) 22, 455–459; doi:10.1038/sj.leu.2404910; published online 23 August 2007 Fully differentiated myeloid cells are derived from a common myeloid precursor, which resides in the bone marrow. Depending on activities of cytokines and transcription factors, the differentiation of the common myeloid precursor gives rise to granulocyte/macrophage progenitors, megakaryocyte/ erythroid progenitors and mast cell/basophil progenitors. 1 The granulocyte/macrophage progenitors further branch into neu- trophilic granulocytes or macrophages, dendritic cells and osteoclasts. 2 The development of dendritic cells is stimulated in the presence of interleukin (IL)-4 and granulocyte/macro- phage colony-stimulating factor (GM-CSF). Interestingly, both GM-CSF and IL-4 are also potent inducers of the recently discovered protein DC-STAMP (dendritic cell specific transmembrane protein). DC-STAMP is a novel 470 amino-acid protein preferentially expressed in myeloid DC, macrophages and osteoclasts. 3–5 DC-STAMP is a conserved multi-membrane spanning protein, with little or no homology to other known proteins. 3,4,6 Although the function of DC-STAMP in DC is unknown, recent data indicate a role for DC-STAMP in macrophage and osteoclast fusion. 5 DC-STAMP mRNA is expressed at very low levels in undifferentiated bone marrow cells and monocytes. Upon differentiation of these cells towards DC or macrophage using IL-4 and GM-CSF, DC-STAMP mRNA levels increase and parallel the increase in the expression of CD11c. 3,4,6 In freshly isolated spleen cells, DC-STAMP mRNA expression is predominantly restricted to CD11c pos cells and is hardly detectable in CD11c neg cells, including granulocytes. 6 Thus, the expression of DC-STAMP appears to be limited to cells belonging to the common myeloid precursor-derived branch that comprises macrophages, DC and osteoclasts and it is not expressed in neutrophilic granulocytes belonging to the other branch. This expression pattern plus the induction of DC-STAMP by IL-4, which controls the branching in granulocyte/macro- phage progenitors development, suggest that DC-STAMP may play a role in the control of myeloid differentiation. We investigated this hypothesis by overexpressing DC-STAMP in murine bone marrow progenitor cells, which were subsequently cultured in various differentiation-inducing conditions. Bone marrow cells were collected from the femurs and tibiae of C57BL6/N female mice as described before. 7 Before retroviral transduction, they were cultured for 2 days in prestimulation medium (Iscove’s modified Dulbecco’s medium (Gibco, Invitro- gen, Carlsbad, CA, USA), 5% fetal calf serum (Intergen, Norcross, GA, USA), 1% bovine serum albumin, 1 mg/ml cytidine, adenosine, uridine, guanosine, 2 0 -deoxycytidine, 2 0 - deoxyadenosine, 2 0 -deoxyguanosine and thymidine, 15 mM cholesterol, 15 mM linolic acid (all from Sigma, St Louis, MO, USA), 50 mM b-mercaptoethanol, 10 mg/ml bovine insulin, antibiotics and antimycotics (all from Gibco)) with growth factors (50 ng/ml murine stem cell factor (SCF), 50 ng/ml human Flt-3L, 10 ng/ml murine IL-12, 10 ng/ml murine IL-3, 10 ng/ml Letters to the Editor 455 Leukemia