Elsevier

Seminars in Oncology

Volume 35, Issue 4, August 2008, Pages 410-417
Seminars in Oncology

Acute myeloid leukemia
Core Binding Factor Acute Myeloid Leukemia

https://doi.org/10.1053/j.seminoncol.2008.04.011Get rights and content

Core binding factor (CBF) acute myeloid leukemia (AML) is cytogenetically defined by the presence of t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), which are found in approximately 15% of all adult de novo AML cases. At the molecular level, both cytogenetic abnormalities result in disruption of CBF, a transcription factor that functions as an essential regulator of normal hematopoiesis. Despite this molecular commonality, recent studies have demonstrated differences in genetic, clinical, and prognostic features between t(8;21) and inv(16)/t(16;16) AML, thereby supporting the notion that they represent two distinct biologic and clinical entities. Furthermore, despite being considered as a more favorable AML risk group, only approximately half of the CBF AML patients are cured with current therapy, indicating the need for improved therapeutic approaches. This review summarizes the most recent laboratory and clinical discoveries relevant to this subset of AML and how they are being applied for in an effort to improve the cure rate in patients with the disease.

Section snippets

Molecular Basis of CBF AML

CBF is a heterodimeric transcription factor complex composed of alpha and beta subunits that plays a pivotal role in normal hematopoiesis.9 The CBF alpha subunit is encoded by one of three homologous genes of the RUNX (Runt-related transcription factor) family, the RUNX1 (AML1; CBFA2; PEBP2aB) gene, whereas the CBF beta subunit is encoded by the CBFB (PEBP2B) gene.9 The CBF alpha subunit binds directly to the DNA promoter sequences of target genes involved in hematopoiesis, whereas the beta

Demographic, Clinical, and Secondary Cytogenetic Characteristics

Although commonly reported together as CBF AML, patients with t(8;21) differ from those with inv(16) AML with regard to demographic and clinical characteristics. The t(8;21) AML patients were found to be less frequently white and more frequently African American than those with inv(16).29, 30 Diagnostic white blood cell counts29, 30, 31 and the percentage of blasts in bone marrow and blood29 are higher in inv(16) compared with t(8;21) AML. The typical French-American-British (FAB) blast

Treatment and Outcomes

The CBF AMLs are commonly classified within the favorable AML risk group. The complete remission (CR) rates in both t(8,21) and inv(16) AML are high and reach approximately 90% after standard induction therapy containing anthracyclines and cytarabine.29, 31 One study reported that higher bone marrow blasts, lower platelets, and non-white race in t(8;21) AML and lower platelets and hepatomegaly in inv(16) AML adversely affected the probability to achieve CR.29 A different study showed that the

Prognostic Genetic Factors

Although in comparison to other cytogenetic AML groups, CBF AML patients are considered as a more favorable subset, improved therapy is needed as 50% of CBF AML patients still are not cured. Genetic markers may be useful to predict poor outcome in CBF AML patients, thereby providing a means for risk-adapted stratification to more aggressive and/or novel targeted therapies for those patients that are predicted not to be cured by chemotherapy alone.

In t(8;21) AML, an earlier German study

Monitoring of Minimal Residual Disease in CBF AML

The term “minimal residual disease” (MRD) refers to the persistence of leukemic cells not detectable by microscopic examination of bone marrow. The ultimate goal of MRD analysis is to anticipate an impending hematological relapse, which would allow a timely therapeutic intervention. The combination of reverse transcription of RNA with subsequent polymerase chain reaction (RT-PCR) enables the amplification of individual RNA sequences such as RUNX1/RUNX1T1 and CBFB/MYH11. However, the

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