Core binding factor (CBF) acute myeloid leukemia: is molecular monitoring by RT-PCR useful clinically?

Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and the fusion proteins RUNX1-RUNX1T1 and CBFB-MYH11. International guidelines recommend monitoring for measurable residual disease every 3 months for 2 years after treatment. However, it is unknown if serial molecular monitoring can predict and prevent morphologic relapse. We conducted a retrospective single-center study of 114 patients in complete remission who underwent molecular monitoring with RT-qPCR of RUNX1-RUNX1T1 or CBFB-MYH11 transcripts every 3 months. Morphologic relapse was defined as re-emergence of >5% blasts and molecular relapse as ≥1 log increase in transcript level between 2 samples. Over a median follow-up time of 3.7 years (range 0.2-14.3), remission persisted in 71 (62.3%) patients but 43 (37.7%) developed molecular or morphologic relapse. Patients who achieved <3 log reduction in RUNX1-RUNX1T1 or CBFB-MYH11 transcripts at end of chemotherapy had a significantly higher risk of relapse compared to patients who achieved ≥3 log reduction (61.1% vs. 33.7%, p=0.004). The majority of relapses (74.4%, n=32) were not predicted by molecular monitoring and occurred rapidly with <100 days from molecular to morphologic relapse. Molecular monitoring enabled the detection of impending relapse and permitted pre-emptive intervention prior to morphologic relapse in only 11 (25.6%) patients. The current practice of molecular monitoring every 3 months provided insufficient lead-time to identify molecular relapses and prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia treated at our institution. Further research is necessary to determine the optimal monitoring strategies for these patients.

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Predictive value of molecular remissions postconsolidation chemotherapy in patients with Core Binding Factor Acute Myeloid Leukemia (CBF-AML) - a single center analysis

Hematological Oncology ◽

10.1002/hon.2341 ◽

2016 ◽

Vol 35 (4) ◽

pp. 810-813 ◽

Cited By ~ 1

Author(s):

Uday Deotare ◽

Marwan Shaheen ◽

Joseph M. Brandwein ◽

Bethany Pitcher ◽

Suzanne Kamel-Reid ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Predictive Value ◽

Myeloid Leukemia ◽

Single Center ◽

Core Binding Factor ◽

Binding Factor ◽

Acute Myeloid

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Minimal residual disease eradication with epigenetic therapy in core binding factor acute myeloid leukemia

American Journal of Hematology ◽

10.1002/ajh.24782 ◽

2017 ◽

Vol 92 (9) ◽

pp. 845-850 ◽

Cited By ~ 18

Author(s):

Brittany Knick Ragon ◽

Naval Daver ◽

Guillermo Garcia-Manero ◽

Farhad Ravandi ◽

Jorge Cortes ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Minimal Residual Disease ◽

Myeloid Leukemia ◽

Residual Disease ◽

Epigenetic Therapy ◽

Core Binding Factor ◽

Disease Eradication ◽

Binding Factor ◽

Minimal Residual ◽

Acute Myeloid

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Molecular and Clinical Advances in Core Binding Factor Primary Acute Myeloid Leukemia: A Paradigm for Translational Research in Malignant Hematology

Cancer Investigation ◽

10.3109/07357900009012209 ◽

2000 ◽

Vol 18 (8) ◽

pp. 768-780 ◽

Cited By ~ 30

Author(s):

Guido Marcucci ◽

Michael A. Caligiuri ◽

Clara D. Bloomfield

Keyword(s):

Acute Myeloid Leukemia ◽

Translational Research ◽

Myeloid Leukemia ◽

Core Binding Factor ◽

Binding Factor ◽

Clinical Advances ◽

Acute Myeloid

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Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: A SEER database analysis

Leukemia Research ◽

10.1016/j.leukres.2014.04.001 ◽

2014 ◽

Vol 38 (7) ◽

pp. 773-780 ◽

Cited By ~ 15

Author(s):

Andrew M. Brunner ◽

Traci M. Blonquist ◽

Hossein Sadrzadeh ◽

Ashley M. Perry ◽

Eyal C. Attar ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Population Based ◽

Seer Database ◽

Database Analysis ◽

Core Binding Factor ◽

Binding Factor ◽

Acute Myeloid

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A Predictor Combining Clinical and Genetic Factors for AML1-ETO Leukemia Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.783114 ◽

2022 ◽

Vol 11 ◽

Author(s):

Min Yang ◽

Bide Zhao ◽

Jinghan Wang ◽

Yi Zhang ◽

Chao Hu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Somatic Mutations ◽

Genetic Factors ◽

Risk Model ◽

Core Binding Factor ◽

Kit Mutation ◽

Binding Factor ◽

Prognostic Prediction ◽

Acute Myeloid

Core Binding Factor (CBF)-AML is one of the most common somatic mutations in acute myeloid leukemia (AML). t(8;21)/AML1-ETO-positive acute myeloid leukemia accounts for 5-10% of all AMLs. In this study, we consecutively included 254 AML1-ETO patients diagnosed and treated at our institute from December 2009 to March 2020, and evaluated molecular mutations by 185-gene NGS platform to explore genetic co-occurrences with clinical outcomes. Our results showed that high KIT VAF(≥15%) correlated with shortened overall survival compared to other cases with no KIT mutation (3-year OS rate 26.6% vs 59.0% vs 69.6%, HR 1.50, 95%CI 0.78-2.89, P=0.0005). However, no difference was found in patients’ OS whether they have KIT mutation in two or three sites. Additionally, we constructed a risk model by combining clinical and molecular factors; this model was validated in other independent cohorts. In summary, our study showed that c-kit other than any other mutations would influence the OS in AML1-ETO patients. A proposed predictor combining both clinical and genetic factors is applicable to prognostic prediction in AML1-ETO patients.

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