A 68-year-old man presents with bleeding manifestations. Peripheral smear shows the presence of cells shown below. Which of the following is the most common chromosomal abnormality seen in this condition?

Explanation

## Correct Answer: C. t(8;21) The peripheral smear findings in a 68-year-old with bleeding manifestations showing abnormal cells point to **acute myeloid leukemia (AML)**. The t(8;21) translocation is the most common chromosomal abnormality in AML, accounting for approximately 5–10% of all AML cases and up to 20% of AML with maturation (FAB M2 subtype). This translocation results in the RUNX1-RUNX1T1 (formerly AML1-ETO) fusion gene, which disrupts normal hematopoietic differentiation and promotes leukemic transformation. The t(8;21) is classified as a **core binding factor (CBF) AML** and is associated with a relatively favorable prognosis compared to other AML subtypes, especially when treated with high-dose cytarabine-based chemotherapy. The bleeding manifestations in this elderly patient reflect thrombocytopenia and coagulopathy secondary to leukemic infiltration and consumption. In Indian clinical practice, AML with t(8;21) is recognized as a distinct entity in the WHO classification and carries prognostic significance for treatment planning. The presence of Auer rods (abnormal myeloid precursors) on the smear would further support this diagnosis. ## Why the other options are wrong **A. t(15;17)** — This is wrong because t(15;17) is the hallmark of **acute promyelocytic leukemia (APL, FAB M3)**, not the most common AML translocation overall. While APL is a distinct AML subtype with excellent prognosis when treated with ATRA and arsenic trioxide, it accounts for only 5–10% of AML cases. The NBE trap here is that APL is highly clinically significant due to its unique treatment and dramatic response, but it is NOT the most common chromosomal abnormality in AML. **B. inv(16)** — This is wrong because inv(16) is another **core binding factor (CBF) AML** translocation (CBFB-MYH11 fusion) seen in AML with abnormal eosinophils (FAB M4Eo), accounting for only 5–8% of AML cases. While it carries favorable prognosis similar to t(8;21), it is less common than t(8;21). The trap is that both are CBF-AML with good prognosis, but the question asks for the MOST common, making t(8;21) the correct answer. **D. t(14;18)** — This is wrong because t(14;18) is the **hallmark translocation of follicular lymphoma (BCL2-IGH fusion)**, not AML. This represents a fundamental category error—the question describes an acute leukemia with bleeding manifestations, not a lymphoid malignancy. The NBE trap exploits students who confuse hematologic malignancies or recall t(14;18) as a 'common translocation' without verifying the disease context. ## High-Yield Facts - **t(8;21)** is the most common chromosomal abnormality in AML, seen in ~5–10% of all AML and ~20% of AML-M2 (AML with maturation). - **Core binding factor (CBF) AML** includes t(8;21) and inv(16); both carry favorable prognosis and respond well to high-dose cytarabine. - **RUNX1-RUNX1T1 fusion** (formerly AML1-ETO) from t(8;21) disrupts transcriptional regulation and is diagnostic for this AML subtype. - **t(15;17)** defines APL (M3), **inv(16)** defines AML-M4Eo, and **t(14;18)** defines follicular lymphoma—each is disease-specific. - **Bleeding manifestations** in AML result from thrombocytopenia, DIC, and leukostasis; t(8;21) AML-M2 often presents with myeloid differentiation. ## Mnemonics **CBF-AML (Core Binding Factor)** **t(8;21)** and **inv(16)** are the two CBF-AML translocations with favorable prognosis. Remember: **8-21 = AML1-ETO** (most common), **inv-16 = CBFB-MYH11** (eosinophils). Use this when you see 'good prognosis AML' or 'favorable cytogenetics.' **AML Translocation Triage** **t(15;17) = APL (M3)**, **t(8;21) = AML-M2 (most common)**, **inv(16) = AML-M4Eo**, **t(9;11) = AML-M5 (monocytic)**. When a question asks 'most common AML translocation,' default to t(8;21) unless APL is explicitly mentioned. ## NBE Trap NBE pairs t(15;17) with 'AML' to trap students who conflate APL's clinical importance and unique treatment with overall frequency. The question's emphasis on 'bleeding manifestations' may also mislead students toward APL (which presents with severe DIC), but t(8;21) AML-M2 is still more common overall. ## Clinical Pearl In Indian tertiary centers, t(8;21) AML-M2 is recognized as a 'favorable-risk' AML subtype eligible for intensive chemotherapy with curative intent, especially in younger patients. Elderly patients like this 68-year-old may still benefit from high-dose cytarabine if fit, making cytogenetic confirmation essential for prognostication and treatment planning. _Reference: Robbins Ch. 13 (Hematopoietic and Lymphoid Neoplasms); Harrison Ch. 104 (Acute Myeloid Leukemia)_