Book1 Gen 2018, 1766(Methods in Molecular Biology book series) .
This detailed volume examines bioinformatic and molecular biological methods useful to identify and to explore the functions of CpG islands, key navigation points to understand gene regulation in fundamental processes such as development and cell differentiation as well as in diseases like cancer. Beginning with a historical perspective and important properties of CpG islands, the book continues with sections on computational and wet lab methods related to the study of DNA methylation, and in-depth protocols for the analysis of CpG island functional features including epigenetic profiling and chromatin interactions. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls.
Authoritative and practical, CpG Islands: Methods and Protocols aims to provide readers with the information and methodologies necessary to continue to decipher how a genome’s structure and organization contribute to regulate biological processes.
Keywords: CpG dinucleotides Gene regulation Bioinformatics Computational methods DNA methylation Epigenetics Chromatin interactions
Sorigue M, Juncà J, Sarrate E, Grau J
Expression of CD43 in chronic lymphoproliferative leukemias.
Cytometry B Clin CytomGen 2018, 94(1)136-142. Epub 25 Gen 2017
CD43 has been used on histological samples for the differential diagnosis of lymphoproliferative disorders but there is scarce data on its use by flow cytometry (FC). We set out to characterize the expression of CD43 by FC in B-cell lymphoproliferative disorders and to determine its possible role in the differential diagnosis of these malignancies.
Motlló C, Ribera JM, Morgades M, Granada I, Montesinos P, Mercadal S, González-Campos J, Moreno MJ, Barba P, Cervera M, Barrios M, Novo A, Bernal T, Hernández-Rivas JM, Abella E, Amigo ML, Tormo M, Martino R, Lavilla E, Bergua J, Serrano A, García-Belmonte D, Guàrdia R, Grau J, Feliu E
Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia.
Leuk. LymphomaGen 2018, 59(1)146-154. Epub 30 Mai 2017
About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.
Martínez-Cuadrón D, Montesinos P, Vellenga E, Bernal T, Salamero O, Holowiecka A, Brunet S, Gil C, Benavente C, Ribera JM, Pérez-Encinas M, De la Serna J, Esteve J, Rubio V, González-Campos J, Escoda L, Amutio ME, Arnan M, Arias J, Negri S, Lowënberg B, Sanz MA
Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy.
LeukemiaGen 2018, 32(1)21-29. Epub 6 Jun 2017
Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.
Palomo L, Malinverni R, Cabezón M, Xicoy B, Arnan M, Coll R, Pomares H, García O, Fuster-Tormo F, Grau J, Feliu E, Solé F, Buschbeck M, Zamora L
DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical, biological and genetic features.
Epigenetics2018, 13(1)8-18. Epub 6 Feb 2018
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation, including hypermethylation of specific genes and large genome regions with aberrant DNA methylation. Unsupervised hierarchical cluster analysis identified two main clusters that associated with the clinical, biological, and genetic features of patients. Group 1 was enriched in patients with adverse clinical and biological characteristics and poorer overall and progression-free survival. In addition, significant differences in DNA methylation were observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild type patients. Taken together, our results demonstrate that altered DNA methylation patterns reflect the CMML disease state and allow to identify patient groups with distinct clinical features.