Eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and affect patient survival. We cloned the t(1;5)(q23;q33) and showed that it fuses platelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel partner protein, myomegalin. Using two-color interphase fluorescence in situ hybridization (FISH), we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started, complete clinical and hematologic remission, as well as major cytogenetic response, was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family. (Blood. 2003;102: 4187-4190)

Background Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained. This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis. The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (>/=30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82-9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87-87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14-108.02). Conclusions The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone.

Background: Few immunohematological studies have been done in myelodysplastic syndrome (MDS). Methods: Twenty-nine MDS patients were retrospectively evaluated with a direct antiglobulin test (DAT), antibody screening, serum electrophoresis and immunoelectrophoresis. Clinical and laboratory studies (hemoglobin level, reticulocyte count, DHL, total and indirect bilirubin) were done simultaneously, as well as the French-American-British subtype and bone marrow biopsy findings. Results: Alloantibodies were demonstrated in 17 patients (58.6%), autoantibodies in 10 (34.4%) patients and cold agglutinin in 18 (62%) patients. DAT was mediated by only IgG in 8 patients (80%), by IgG and C3 in 1 patient (10%) and by IgG, IgA and C3 in 1 (10%) patient. No hemolytic disease occurred in patients with autoantibodies. Increased serum gammaglobulin was observed in 16 (54.4%) patients. There was no correlation between the incidence of allo-/autoantibodies and the gammaglobulin level (p = 0.937) and the presence of lymphocyte infiltrates in bone marrow biopsies (p = 0.156). No significant difference was observed when the incidence of autoantibodies and number of red blood cell transfusions were compared (p = 0.334). Patients with refractory anemia and refractory anemia with ringed sideroblasts subtypes had a higher incidence of allo-/autoantibodies than other MDS subtypes (p = 0.03). Conclusion: Patients with MDS, in particular refractory anemia and refractory anemia with ringed sideroblasts have a high incidence of allo- and autoantibodies, probably related to intrinsic immune disorder, without clinical or laboratory hemolysis.