Extensive myocardial infiltration by hemopoietic precursors in a patient with myelodysplastic syndrome

BACKGROUND: Although myocardial infiltration with leukemic blasts is a known finding in patients with acute leukemia, this phenomenon in myelodysplasia is not reported in the literature. Cardiac symptoms in patients with myelodysplasia are often due to anemia and may be due to iron overload and side effects of therapy. CASE PRESENTATION: Herein we report the first case of neoplastic infiltration of the heart with associated myocardial necrosis in a patient with myelodysplasia. It was associated with unicellular and multifocal geographic areas of necrosis in the left ventricle and the interventricular septum. It is likely that cardiac compromise in our patient was due to a combination of restrictive cardiomyopathy due to leukemic infiltration, concomitant anemia, cardiac dilatation, conduction blocks and myocardial necrosis. Myocardial necrosis was most likely due to a combination of ischemic damage secondary to anemia and prolonged hypotension and extensive leukemic infiltration. Markedly rapid decrease in ejection fraction from 66% to 33% also suggests the role of ischemia, since leukemic infiltration is not expected to cause this degree of systolic dysfunction over a 24-hour period. The diagnosis was not suspected during life due to concomitant signs and symptoms of anemia, pulmonary infections, and pericardial and pleural effusions. The patient succumbed to cardiac failure. CONCLUSION: Hemopoietic cell infiltration was not considered in the differential diagnosis and contributed to this patient's morbidity and mortality. This case highlights the clinical importance of considering myocardial infiltration in patients with myelodysplasia and cardiac symptoms

In Vitro Transformation of Primary Human CD34+ Cells by AML Fusion Oncogenes: Early Gene Expression Profiling Reveals Possible Drug Target in AML

Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of 4 major groups of AML fusion oncogenes on primary human CD34+ cells. As expected from their clinical similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They both caused erythroid hyperplasia and a clear block in erythroid and myeloid maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a dramatic increase in long-term proliferation and self-renewal. Gene expression profiling revealed two distinct temporal patterns of gene deregulation. Gene deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA occurred within 6 hours, followed by a dramatic drop in the numbers of deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1-ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53, specifically inhibited the proliferation and self-renewal of primary human CD34+ cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in cell transformation by AML1-ETO. These data show that differences among AML fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells and that early gene expression profiling in these cells can reveal potential drug targets in AML

Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol

We reviewed and categorized 638 of 809 patients who were registered in the Japan Adult Leukemia Study Group acute myeloid leukemia (AML)-97 protocol using morphological means. Patients with the M3 subtype were excluded from the study group. According to the WHO classification, 171 patients (26.8%) had AML with recurrent genetic abnormalities, 133 (20.8%) had AML with multilineage dysplasia (MLD), 331 (51.9%) had AML not otherwise categorized, and 3 (0.5%) had acute leukemia of ambiguous lineage. The platelet count was higher and the rate of myeloperoxidase (MPO)-positive blasts was lower in AML with MLD than in the other WHO categories. The outcome was significantly better in patients with high (≥50%) than with low (<50%) ratios of MPO-positive blasts (P < 0.01). The 5-year survival rates for patients with favorable, intermediate, and adverse karyotypes were 63.4, 39.1, and 0.0%, respectively, and 35.5% for those with 11q23 abnormalities (P < 0.0001). Overall survival (OS) did not significantly differ between nine patients with t(9;11) and 23 with other 11q23 abnormalities (P = 0.22). Our results confirmed that the cytogenetic profile, MLD phenotype, and MPO-positivity of blasts are associated with survival in patients with AML, and showed that each category had the characteristics of the WHO classification such as incidence, clinical features, and OS

Writing week-journals to improve the writing quality of fourth-graders' compositions

Students' writing problems are a global educational concern and is in need of particular attention. This study aims to examine the impact of providing extra writing opportunities (i.e., writing journals) on the quality of writing compositions. A longitudinal cluster-randomized controlled design using a multilevel modeling analysis with 182 fourth grade students was conducted. We examined whether students' writing quality differed when writing journals on a weekly basis for 12 weeks, compared with a control group. Three covariates were analyzed, namely: (i) the students' attitudes towards writing; (ii) their self-efficacy in writing; (iii) and their use of self-regulation (SRL) strategies while writing. Findings have shown that students who wrote week-journals significantly improved the writing quality of their compositions and reported a higher use of SRL strategies in writing. Nevertheless, self-efficacy and attitude towards writing were found to not be related to the quality of the compositions. Moreover, data indicated that the writing quality of compositions improved along with the writing quality of the week-journals. Findings suggest the use of week-journals in class to promote writing.(undefined)info:eu-repo/semantics/publishedVersio

Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group

Item does not contain fulltextFlow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique.1 juli 201