Influence of cytogenetic abnormalities on outcome after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission

AbstractCytogenetic abnormalities detected at diagnosis are recognized as important in predicting response to chemotherapy in acute myeloid leukemia (AML). However, there is controversy concerning the prognostic significance of karyotype for outcome after allogeneic bone marrow transplantation (allo-BMT) performed in first complete remission (CR1). This single-institution report describes allo-BMT for AML in CR1 and the effect of diagnostic cytogenetic findings on the results of that treatment. Between August 1981 and December 1999, 93 patients underwent related donor (n = 82) or unrelated donor (n = 11) BMT. Conditioning and GVHD prophylaxis were achieved predominantly with busulfan and cyclophosphamide and with cyclosporine and methotrexate, respectively. Seventy-nine (85%) of 93 patients had successful marrow karyotyping at diagnosis, and the patients were categorized into 3 prognostic groups based on the British Medical Research Council AML 10 trial classification: 15 patients(19%) were classified as having favorable risk [inv(16), t(8;2 1), t(15;17)]; 55 (70%) as having intermediate risk [no abnormality, +8, +21, +22, del(7q), del(9q), 11q23 rearrangement, and other numerical or structural abnormalities]; and 9 (11%) as having adverse risk [-5, del(5q), -7, 3q rearrangements, > or = 5 abnormalities, t(6;9), t(9;22)]. The median follow-up was 93 months (range, 16-241 months). The overall survival (OS) rate, event-free survival (EFS) rate, relapse rate, and treatment-related mortality (TRM) were not statistically different between the groups. The 5-year actuarial EFS rates for favorable, intermediate, and adverse risk groups were 58% (95% confidence interval [CI], 29%-79%), 58% (95% CI, 43%-70%), and 67% (95% CI 28%-88%), respectively. Reclassification of patients into cytogenetic prognostic subgroups according to Southwest Oncology Group criteria did not change these results. In univariate analysis, the only variable found to have a prognostic influence on OS (P = .04) and TRM (P = .03) was the type of donor (unrelated donor was linked to a worse prognosis), which was confirmed in multivariate analysis. Our study suggests that presentation karyotype has less prognostic significance for outcome following allo-BMT than for outcome following conventional chemotherapy. In particular, AML patients with poor prognostic cytogenetic changes in CR1 who are unlikely to be cured with chemotherapy alone may benefit from allo-BMT.Biol Blood Marrow Transplant 2002;8(8):435-43

The global prevalence of Huntington’s disease: a systematic review and discussion

The ascertained prevalence of Huntington's disease (HD) increased significantly following the provision of diagnostic testing. A systematic review was conducted to estimate the prevalence of HD in the post-diagnostic testing era. Twenty-two studies with original data pertaining to the prevalence of HD (1993–2015) were included and analyzed. A global meta-analysis was not performed due to heterogeneity in study methods and geographical variation. The prevalence of HD is significantly lower in Asian populations compared with western Europe, North America and Australia. The global variation in HD prevalence is partly explained by the average CAG repeat lengths and frequency of different HTT gene haplotypes in the general population. Understanding the prevalence of HD has significant implications for healthcare resource planning

Quality of life in couples living with Huntington’s disease: the role of patients’ and partners’ illness perceptions

Research suggests that chronically ill patients and their partners perceive illness differently, and that these differences have a negative impact on patients’ quality of life (QoL). This study assessed whether illness perceptions of patients with Huntington’s disease (HD) differ from those of their partners, and examined whether spousal illness perceptions are important for the QoL of the couples (n = 51 couples). Partners reported that their HD-patient spouses suffered more symptoms and experienced less control than the patients themselves reported. Illness perceptions of patients and partners correlated significantly with patient QoL. Partners’ beliefs in a long duration of the patients’ illness and less belief in cure, were associated with patient vitality scores. Suggestions for future research emphasize the importance of qualitative research approaches in combination with cognitive-behavioural approaches

Genetic aspects of dental disorders

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.This paper reviews past and present applications of quantitative and molecular genetics to dental disorders. Examples are given relating to craniofacial development (including malocclusion), oral supporting tissues (including periodontal diseases) and dental hard tissues (including defects of enamel and dentine as well as dental caries). Future developments and applications to clinical dentistry are discussed. Early investigations confirmed genetic bases to dental caries, periodontal diseases and malocclusion, but research findings have had little impact on clinical practice. The complex multifactorial aetiologies of these conditions, together with methodological problems, have limited progress until recently. Present studies are clarifying previously unrecognized genetic and phenotypic heterogeneities and attempting to unravel the complex interactions between genes and environment by applying new statistical modelling approaches to twin and family data. linkage studies using highly polymorphic DNA markers are providing a means of locating candidate genes, including quantitative trait loci (QTL). In future, as knowledge increases: it should be possible to implement preventive strategies for those genetically-predisposed individuals who are identified-predisposed individuals who are identified to be at risk.Grant C. Townsend, Michael J. Aldred and P. Mark Bartol

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

Myelodysplastic Syndrome/Acute Myeloid Leukemia Arising in Idiopathic Erythrocytosis

The term “idiopathic erythrocytosis (IE)” is applied to those cases where a causal clinical or pathological event cannot be elucidated and likely reflects a spectrum of underlying medical and molecular abnormalities. The clinical course of a patient with IE is described manifesting as a persistent erythrocytosis with a low serum erythropoietin level, mild eosinophilia, and with evidence of a thrombotic event. The patient subsequently developed a myelodysplasic syndrome (MDS) and acute myeloid leukemia (AML), an event not observed in erythrocytosis patients other than those with polycythemia vera (PV). Application of a next-generation sequencing (NGS) approach targeted for myeloid malignancies confirmed wild-type JAK2 exons 12–15 and identified a common SH2B3 W262R single-nucleotide polymorphism associated with the development of hematological features of myeloproliferative neoplasms (MPNs). Further NGS analysis detected a CBL L380P mutated clone expanding in parallel with the development of MDS and subsequent AML. Despite the absence of JAK2, MPL exon 10, or CALR exon 9 mutations, a similarity with the disease course of PV/MPN was evident. A clonal link between the erythrocytosis and AML could be neither confirmed nor excluded. Future molecular identification of the mechanisms underlying IE is likely to provide a more refined therapeutic approach