The insulin gene is specifically expressed in ␤-cells of the Langerhans islets of the pancreas, and its transcription is regulated by the circulating glucose level. Previous reports have shown that an unidentified ␤-cell-specific nuclear factor binds to a conserved cis-regulatory element called RIPE3b and is critical for its glucose-

The online version of this article has a Supplementary Appendix. BackgroundThe current World Health Organization classification of myelodysplastic syndromes is based on morphological evaluation of bone marrow dysplasia. In clinical practice, the reproducibility of the recognition of dysplasia is usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities. Design and MethodsWe aimed to develop and validate a flow cytometric score for the diagnosis of myelodysplastic syndrome. Four reproducible parameters were analyzed: CD34 + myeloblast-related and B-progenitor-related cluster size (defined by CD45 expression and side scatter characteristics on CD34 + marrow cells), myeloblast CD45 expression and granulocyte side scatter value. The study comprised a "learning cohort" (n=538) to define the score and a "validation cohort" (n=259) to confirm its diagnostic value. ResultsWith respect to non-clonal cytopenias, patients with myelodysplastic syndrome had increased myeloblast-related cluster size, decreased B-progenitor-related cluster size, aberrant CD45 expression and reduced granulocyte side scatter (P<0.001). To define the flow cytometric score, these four parameters were combined in a regression model and the weight for each variable was estimated based on coefficients from that model. In the learning cohort a correct diagnosis of myelodysplastic syndrome was formulated in 198/281 cases (sensitivity 70%), while 18 false-positive results were noted among 257 controls (specificity 93%). Sixty-five percent of patients without specific markers of dysplasia (ring sideroblasts and clonal cytogenetic abnormalities) were correctly classified. A high value of the flow cytometric score was associated with multilineage dysplasia (P=0.001), transfusion dependency (P=0.02), and poor-risk cytogenetics (P=0.04). The sensitivity and specificity in the validation cohort (69% and 92%, respectively) were comparable to those in the learning cohort. The likelihood ratio of the flow cytometric score was 10. ConclusionsA flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate. LeukemiaNET study. Haematologica 2012;97(8):1209-1217. doi:10.3324/haematol.2011 This is an open-access paper. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

We conducted a multi-institutional randomized study to determine whether highdose daunorubicin would be as effective as standard-dose idarubicin in remissioninduction therapy for newly diagnosed adult patients younger than 65 years of age with acute myeloid leukemia. Of 1064 patients registered, 1057 were evaluable. They were randomly assigned to receive either daunorubicin (

BACKGROUND.Although studies comparing conventional imaging modalities with 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) for the detection of lymphoma and although the relations between 18F‐FDG‐PET and histologic types were reported previously, most studies were not systematic and involved relatively small numbers of patients.METHODS.Two hundred fifty‐five patients with lymphoma had their disease staged using 18F‐FDG‐PET, and 191 of those patients also were assessed using gallium‐67 scintigraphy (67Ga). Disease sites were identified on a site‐by‐site basis using computed tomography scans and/or magnetic resonance imaging. The results of these conventional imaging modalities were compared with the results from 8F‐FDG‐PET and 67Ga, and correlations between the imaging results and pathologic diagnoses were evaluated by using the World Health Organization classification system.RESULTS.Of 913 disease sites in 255 patients, 18F‐FDG‐PET identified >97% of disease sites of Hodgkin lymphoma (HL) and aggressive and highly aggressive non‐Hodgkin lymphoma. For indolent lymphoma, the detection rate of 18F‐FDG‐PET was 91% for follicular lymphoma (FL); 82% for extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue, irrespective of plasmacytic differentiation; and approximately 50% for small lymphocytic lymphoma (SLL) and splenic marginal zone lymphoma (SMZL). The results from 67Ga were similar to those from 18F‐FDG‐PET for most histologic subtypes. However, the sensitivity of 67Ga was unexpectedly poor for FL, for mantle cell lymphoma (MCL), and for the nasal type of natural killer/T‐cell lymphoma (NK/T‐nasal), ranging from 30% to 38%.CONCLUSIONS.18F‐FDG‐PET was useful for all histologic subtypes of lymphoma other than SLL and SMZL. Compared with 67Ga, the authors strongly recommend the use of 18F‐FDG‐PET in patients with FL, MCL, and NK‐nasal. Cancer 2007. © 2007 American Cancer Society.

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by increased platelet clearance because of antiplatelet antibodies. It was recently reported that the balance of T helper 1 (Th1) and T helper 2 (Th2) subsets has been implicated in the regulation of many immune responses. In this study, the intracellular interleukin-4 and interferon-gamma production in CD4+ T-lymphocytes activated by phorbol 12-myristate 13-acetate and ionomycin was assessed via flow cytometry in order to determine the clinical significance of the Th1/Th2 ratio in 42 patients with ITP. The study cohort included 28 untreated patients, seven postprednisolone therapy patients and seven postsplenectomy patients. The mean level of the Th1/Th2 ratio in the untreated group was 36.9 (95% CI 25.8-47.9), and significantly higher than in the control group (mean 12.8, 95% CI 9.5-16.1). The mean levels of the Th1/Th2 ratio in the postprednisolone therapy and postsplenectomy groups were 20.5 (95% CI 8.4-32.6) and 16.4 (95% CI 3.1-29.7), respectively, but were no significant differences as compared with control subjects. When untreated patients were divided into two subgroups by Th1/Th2 ratio, the mean level of platelet associated IgG in the high Th1/Th2 subgroup (higher than upper limit of control group) tended to be higher than in the normal Th1/Th2 subgroup. In conclusion, the high Th1/Th2 ratio was closely related to the etiology and disease status of chronic ITP.