Abstract IA01: Clinical significance of molecular findings in acute myeloid leukemia.
Authors: Bloomfield Clara D. 
Published: August 2015

Acute myeloid leukemia (AML) is a very heterogeneous disease. Cytogenetics and molecular findings are currently the most important factors for selecting therapy. They allow improved diagnosis, prognosis, and therapy. Their importance in diagnosis is reflected in the current World Health Organization (WHO) classification,(1) which first identifies specific types of AML by specific recurrent genetic abnormalities; in a number of genetic subtypes the diagnosis is AML regardless of percent blasts. The 2008 WHO classification includes, for the first time, provisional entities based solely on molecular findings, and overall increases the percent of AML genetically classified from ~30% in the last classification (in 2001) to more than 75%. The 2008 version of the WHO classification is currently undergoing revision with planned publication in 2015. It is likely to further expand the use of cytogenetics and molecular findings for classification.

Currently only one of the WHO genetic subtypes is managed almost totally based on molecular markers: acute promyelocytic leukemia (APL). This has changed the outcome for APL patients from a median survival of two weeks to a cure rate of more than 90%. Increasingly two other genetic subtypes,—those with t(8;21)(q22;q22) or inv(16)(p13.1q22) or t(16;16)(p13.1;q22) that are collectively designated core-binding factor AML —which make up ~15% of AML, are being separated from other types of AML and treated using molecularly targeted therapy. Early results from on-going trials suggest improved outcome.

For the remaining types of primary AML, cytogenetics and molecular genetics are the most important prognostic findings and are often used to determine therapy. Approximately 45% of AML cases are cytogenetically normal (CN-AML); numerous molecular abnormalities have been identified in CN-AML that are highly prognostic and increasingly being used to select therapy. The therapy is increasingly molecularly targeted when feasible. Recently, international guidelines for reporting clinical data in AML have mandated correlation with cytogenetic and molecular genetic data.(2) Studies of the prognostic use of the European LeukemiaNet guidelines have demonstrated it's significant correlation with outcome.

Treatment trials for about two-thirds of AML are currently genotype/molecular specific. Early data suggest that as a result we are increasing the percent of cured adult patients, especially those under the age of 60 years.

References:

1. Swerdlow SH, Campo E, Harris NL, et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IACRC; 2008.

2. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453-474.

Citation Format: Clara D. Bloomfield. Clinical significance of molecular findings in acute myeloid leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA01.