Which is the most common cytogenetic abnormality in adult acute myeloid leukemia (AML)?

Explanation

## Cytogenetics of Adult AML **Key Point:** Complex karyotype (defined as ≥ 3 unrelated cytogenetic abnormalities) is the single most common cytogenetic finding in adult AML, occurring in approximately 10–15% of cases. However, when considering balanced translocations, t(8;21) and inv(16) (collectively termed "core binding factor" AML) are the most frequent recurrent abnormalities. ### Frequency of Cytogenetic Abnormalities in Adult AML | Abnormality | Frequency | Prognosis | WHO Classification | |---|---|---|---| | Complex karyotype | 10–15% | Adverse | AML with complex karyotype | | t(8;21) RUNX1-RUNX1T1 | 5–10% | Favorable | AML with t(8;21) | | inv(16) CBFB-MYH11 | 5–8% | Favorable | AML with inv(16) | | t(15;17) PML-RARA | 5–8% | Favorable (with ATRA + arsenic) | APL | | Monosomy 7 / del(7q) | 5–10% | Adverse | AML with monosomy 7 | | TP53 mutations / del(17p) | 5–10% | Adverse | AML with TP53 mutation | | Normal karyotype | 40–50% | Intermediate (depends on FLT3-ITD, NPM1) | AML with normal karyotype | **High-Yield:** The 2022 WHO Classification emphasizes that cytogenetics and molecular mutations (FLT3-ITD, NPM1, CEBPA, TP53) are critical for risk stratification in AML. Complex karyotype is an independent adverse prognostic factor. ### Core Binding Factor (CBF) AML - **t(8;21):** AML-M2 (AML with maturation); RUNX1-RUNX1T1 - **inv(16) or t(16;16):** AML-M4Eo (AML with eosinophilia); CBFB-MYH11 - **Favorable prognosis:** 5-year survival 50–60% with intensive chemotherapy - **Sensitive to high-dose cytarabine** **Clinical Pearl:** Patients with t(15;17) (APL) have an excellent prognosis (> 80% cure rate) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), even though the karyotype itself is not "favorable" by traditional criteria. This is a paradigm shift in AML management. **Mnemonic: "RUNX CBF"** — Remember t(8;21) and inv(16) as the favorable **C**ore **B**inding **F**actor abnormalities; RUNX1 is the gene in t(8;21).