Giles Best

Fludarabine Nucleoside Modulates Nuclear “Survival and Death” Proteins in Resistant Chronic Lymphocytic Leukemia Cells

The nuclear mechanisms by which fludarabine nucleoside (F-ara-A) induces apoptosis have been investigated in human MEC1 cells derived from B-cell chronic lymphocytic leukemia. Upon treatment of cells with F-ara-A (100 μM, 72 hours), 15 nuclear proteins changed in abundance by more than 2-fold. Nuclear proteins up-regulated included calmodulin (4.3-fold), prohibitin (3.9-fold), β-actin variant (3.7-fold), and structure-specific recognition protein 1 (3.7-fold); those down-regulated included 60S ribosomal protein P2B (0.12-fold), fumarate hydratase (0.19-fold), splicing factor arginine/serine-rich 3 (0.35-fold), and replication protein A2 (0.42-fold). These changes in the levels of specific proteins promote survival or apoptosis; because the end result is apoptosis of MEC1 cells, apoptotic effects predominate.

Diagnostic techniques and therapeutic challenges in patients with TP53 dysfunctional chronic lymphocytic leukemia

Abstract Aberrations of the TP53 pathway, whether by deletion or mutation, are increasingly recognized as one of the most important biological risk factors in chronic lymphocytic leukemia. Yet, there is little consensus on how to assess for TP53 defects in the clinic, and very few clinical studies to guide optimal management of such patients. In this review, we discuss the state-of-the-art in the assessment of the TP53 pathway, and review the evidence-base for therapeutic recommendations.

Lymphoma cell-of–origin assignment by gene expression profiling is clinically meaningful across broad laboratory contexts

Beutler, E., Felitti, V., Gelbart, T. & Ho, N. (2000) The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Annals of Internal Medicine, 133, 329–337. Burke, W., Imperatore, G., Mcdonnell, S.M., Baron, R.C. & Khaury, M.J. (2000) Contribution of different HFE genotypes to iron overload disease: a pooled analysis. Genetics in Medicine, 2, 271–277. Feeney, G.P., Carter, K., Masters, G.S., Jackson, H.A., Cavil, I. & Worwood, M. (2005) Changes in erythropoiesis in hereditary hemochromatosis are not mediated by HFE expression in nucleated red cells. Haematologica, 90, 180–187. Lucotte, G. & Mercier, G. (2000) Celtic origin of the C282Y mutation of hemochromatosis. Genetic Testing, 4, 163–169. McMullin, M.F. (2012) Diagnosis and management of congenital and idiopathic erythrocytosis. Therapeutic Advances in Hematology, 3, 391–398. Merryweather-Clarke, A.T., Pointon, J.J., Shearman, J.D. & Robson, K.J.H. (1997) Global prevalence of putative haemochromatosis mutations. Journal of Medical Genetics, 34, 275–278. Olynyk, J.K., Cullen, D.J., Aquilla, S., Rosse, E., Summerville, L. & Powell, L.W. (1999) A population-based study of the clinical expression of the hemochromatosis gene. New England Journal of Medicine, 341, 718–724. Randi, M.L., Bertozzi, I., Cosi, E., Santarossa, C., Peroni, E. & Fabris, F. (2015) Idiopathic erythrocytosis: a study of a large cohort with a long follow-up. Annals of Hematology, 95, 233–237. Raphael, B., Cooperberg, A.A. & Niloff, P. (1979) The triad of hemochromatosis, hepatoma and erythrocytosis. Cancer, 43, 690–694. Yun, S. & Vincelette, N.D. (2015) Update on iron metabolism and molecular perspective of common genetic and acquired disorder, hemochromatosis. Critical Reviews in Oncology/ Hematology, 95, 12–25.