Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Area of Science:

• Hematology
• Cytogenetics
• Oncology

Background:

• Core-binding factor acute myeloid leukemia (CBF-AML) subtypes, t(8;21) and inv(16), exhibit distinct clinical behaviors.
• Despite favorable initial responses, a significant proportion of CBF-AML patients experience relapse, necessitating a deeper understanding of prognostic factors.
• Existing literature suggests differential outcomes between t(8;21) and inv(16) CBF-AML, but the role of additional cytogenetic aberrations requires further elucidation.

Purpose of the Study:

• To investigate the impact of additional cytogenetic aberrations on clinical outcomes in a large cohort of CBF-AML patients.
• To compare the frequency of specific chromosomal abnormalities between t(8;21) and inv(16) CBF-AML subtypes.
• To identify cytogenetic markers that predict overall survival (OS) and disease-free survival (DFS) in CBF-AML.

Main Methods:

• Retrospective analysis of 537 patients diagnosed with CBF-AML.
• Detailed examination of cytogenetic data, including specific chromosomal aberrations like trisomies, deletions, and sex chromosome loss.
• Multivariable analyses were performed, adjusting for age, white blood cell count, and KIT mutation status.

Main Results:

• Trisomies 8, 21, and 22 were more frequent in inv(16)/t(16;16), while del(9q) and sex chromosome loss were more common in t(8;21).
• Hyperdiploidy was more prevalent in inv(16), whereas hypodiploidy was more frequent in t(8;21).
• Trisomy 8 improved OS in inv(16); other aberrations worsened OS. Hypodiploidy improved DFS, and hyperdiploidy/del(9q) improved OS in t(8;21). KIT mutations impacted prognosis only in t(8;21) on univariate analysis.

Conclusions:

• Additional cytogenetic aberrations play a critical role in determining clinical outcomes for both t(8;21) and inv(16) CBF-AML subtypes.
• Specific chromosomal abnormalities, such as trisomy 8 in inv(16) and hypodiploidy/del(9q) in t(8;21), are associated with improved survival.
• These findings underscore the importance of comprehensive cytogenetic analysis for risk stratification and personalized treatment of CBF-AML patients.