T he efficacy of azacitidine in patients with anemia and with lowerrisk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one "epigenetic mutation" and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352).

An Oxford Instruments Radiox cryogenic radiometer was recently installed at the Bureau International des Poids et Mesures (BIPM). The first measurements were aimed at characterizing the performance of the system. The Radiox was then compared with the cryogenic radiometer of the French Institut National de Métrologie (INM), a CRI LaseRad, at the BIPM by successive measurements of the power in a laser beam at two wavelengths: 647 nm and 476 nm. The radiometers differed in these measurements by 1,9 parts in 10 4 , the uncertainties in each being smaller than 1 part in 10 4 .

The parametric down conversion of photons generated in a non-linear crystal gives rise to two correlated photons. When associated with a system of coincidence counting, this phenomenon allows one to measure the quantum efficiencies of detectors working at a normal rate of photon counting, without the need for reference sources or detectors. At the Institut National de Métrologie (INM) (France), this method was implemented with the aim of developing a new standard detector for the absolute measurement of very weak radiation. The validation of this method is presented from an international comparison between the laboratories of the INM (France) and the Istituto Elettrotecnico Nazionale Galileo Ferraris (IENGF) (Italy) and from a comparison of methods at INM using the French national standard detector, the cryogenic radiometer.

Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells and interacts directly with JAK2/STAT5. We also show that its expression is increased in both CD34+ circulating progenitors and in the serum of patients with JAK2-dependent myeloproliferative neoplasms with fibrosis. Our data suggest that HSP27 plays a key role in the pathophysiology of myelofibrosis and represents a new potential therapeutic target for patients with myeloproliferative neoplasms.