Genetic correlates in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with Hyper-CVAD/Hyper-CMAD plus dasatinib or Hyper-CVAD plus ponatinib

Department of Leukemia Research Department of Leukemia Department of Genomic Medicinehttps://openworks.mdanderson.org/edwk21/1004/thumbnail.jp

OncoLog Volume 43, Number 06, June 1998

New treatment strategies improve prognosis in patients with chronic leukemias Ultrasonography fosters targeted intraprostatic therapy Protocols: Trials for Chronic Leukemia Feature Chemotherapy and “Mini” Transplants House Call: Answering the Who, What, When, Why, and How of Cancer DiaLog: Leukemia’s Lessons in Malignant Transformation, by Hagop Kantarjian, MD, Professor of Medicine, Department of Leukemiahttps://openworks.mdanderson.org/oncolog/1063/thumbnail.jp

Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet

Purpose: To review and update the European LeukemiaNet (ELN) recommendations for the management of chronic myeloid leukemia with imatinib and second-generation tyrosine kinase inhibitors (TKIs), including monitoring, response definition, and first- and second-line therapy. Methods: These recommendations are based on a critical and comprehensive review of the relevant papers up to February 2009 and the results of four consensus conferences held by the panel of experts appointed by ELN in 2008. Results: Cytogenetic monitoring was required at 3, 6, 12, and 18 months. Molecular monitoring was required every 3 months. On the basis of the degree and the timing of hematologic, cytogenetic, and molecular results, the response to first-line imatinib was defined as optimal, suboptimal, or failure, and the response to second-generation TKIs was defined as suboptimal or failure. Conclusion: Initial treatment was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.Michele Baccarani, Jorge Cortes, Fabrizio Pane, Dietger Niederwieser, Giuseppe Saglio, Jane Apperley, Francisco Cervantes, Michael Deininger, Alois Gratwohl, François Guilhot, Andreas Hochhaus, Mary Horowitz, Timothy Hughes, Hagop Kantarjian, Richard Larson, Jerald Radich, Bengt Simonsson, Richard T. Silver, John Goldman and Rudiger Hehlman

Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia

BACKGROUND: Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS: We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS: AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS: We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.) Copyright © 2013 Massachusetts Medical Society