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Giants

Role of Genetic Testing in Myelodysplastic Syndromes

Panelists: Rafael Bejar, MD, PhD, UCSD; Harry P. Erba, MD, PhD, UAB; Elias J. Jabbour, MD, MD Anderson;
Rami S. Komrokji, MD, Moffitt; Mark J. Levis, MD, PhD, Johns Hopkins; Ruben A. Mesa, MD, Mayo Clinic
 
Published Online: Tuesday, March 25, 2014
For High-Definition, Click
Genetic analyses are beginning to play a larger role in the diagnosis and determination of prognosis for patients with myelodysplastic syndrome (MDS). However, these assays should still be viewed alongside traditional blood and bone marrow test results, since genetic similarities exist between MDS, acute myeloid leukemia (AML), and certain lymphomas, notes Rafael Bejar, MD, PhD.

Certain cytogenetic abnormalities are associated with MDS by World Health Organization classification, such as 5q deletions. Moreover, Bejar notes, certain splicing factor mutations, such as those in SRSF2, SF3B1, and U2AF1, are more enriched in patients with MDS than those with AML and chronic myeloid leukemia (CML). For patients with an uncertain diagnosis, genetic testing can be utilized as a confirmation. Moreover, in patients with a confirmed diagnosis of MDS, specific mutations could help determine prognosis and the aggressiveness of therapy.

At this point, the predictive value of these genetic signatures is best utilized in low-risk patients, believes Rami S. Komrokji, MD, since the integration of molecular data results in the upstaging of approximately 20% to 30% of patients with low-risk MDS. This upstaging is particularly true when using the International Prognostic Scoring System, notes Bejar. The addition of markers such as ferritin, LDH, and mutations can result in a diagnosis of more advanced disease, especially within the intermediate category.

In terms of treatment, these genetic mutations should be viewed with reservation until further clinical data is available, warns Bejar. In some situations, the mutations that predict more aggressive disease may also predict resistance to therapy, suggesting that earlier treatment may not necessarily lead to better outcomes, Bejar states.
View More From This Discussion
Episode 1 Introduction: Treatment Landscape of MDS
Episode 2 Discontinuation of Treatment With TKIs in CML
Episode 3 Frontline Treatment of Chronic Myelogenous Leukemia
Episode 4 Second-Generation Tyrosine Kinase Inhibitors in CML
Episode 5 Treatment Selection for Resistant or Intolerant CML
Episode 6 Hypomethylating Agents in the Treatment of High-Risk MDS
Episode 7 Role of Genetic Testing in Myelodysplastic Syndromes
Episode 8 Defining and Predicting Response to HMAs in MDS
Episode 9 Treatment of MDS Refractory to Hypomethylating Agent
Episode 10 Current and Future Treatment Landscape for MDS
Episode 11 Novel Agents and Treatment Strategies in MDS
Episode 12 Oral Azacitidine and Lenalidomide Combinations in MDS
Episode 13 Final Thoughts on Clinical Advances in MDS and CML
Expert Panelists
Harry Erba Moderator

Harry P. Erba, MD, PhD

Editor-in-Chief,
Professor of Internal Medicine
Director of Hematologic Malignancy Program
University of Alabama
Birmingham, Alabama
 
 

Mark J. Levis, MD, PhD

Director, Adult Leukemia Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland

Elias J. Jabbour, MD

Associate Professor,
Department of Leukemia,
Division of Cancer Medicine,
MD Anderson Cancer Center, Houston, Texas

Rami S. Komrokji, MD

Clinical Director, Associate Member, Department of Malignant Hematology
H Lee Moffitt Cancer Center
Tampa, Florida
 

Ruben A. Mesa, MD

Chair, Division of Hematology
& Medical Oncology, Mayo Clinic, Scottsdale, Arizona

Rafael Bejar, MD, PhD

Assistant Professor of Medicine, Division of Hematology-Oncology
University of California, San Diego, La Jolla, California
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