A 64-year-old man presents to the emergency department with a 3-week history of progressive fatigue, shortness of breath on exertion, and intermittent fevers. He also notes that his gums have been bleeding easily when he brushes his teeth. On physical examination, he is pale and has scattered petechiae over his upper extremities. There is no significant lymphadenopathy or hepatosplenomegaly.
Laboratory studies show the following:
Hemoglobin: 8.2 g/dL
Platelet count: 28,000/μL
White blood cell count: 52,000/μL
Peripheral blood smear: 65% large cells with abundant cytoplasm, fine chromatin, and prominent nucleoli. Several cells contain thin, needle-like eosinophilic cytoplasmic inclusions.
Myeloperoxidase (MPO) stain: Positive
Which of the following cytogenetic abnormalities is associated with the specific morphological finding described in this patient's peripheral smear?
The correct answer is:
C) t(15;17) translocation
This patient is presenting with acute myelogenous leukemia (AML), specifically the acute promyelocytic leukemia (APL) subtype (formerly M3). AML is characterized by the malignant proliferation of myeloblasts that crowd out normal hematopoiesis, leading to anemia, thrombocytopenia, and neutropenia. The thin, needle-like eosinophilic cytoplasmic inclusions described are Auer rods, which are crystallized granules of myeloperoxidase (MPO). While Auer rods can be seen in various types of AML, they are especially numerous in APL.
The t(15;17) translocation involves the fusion of the PML (promyelocytic leukemia) gene on chromosome 15 and the RARA (retinoic acid receptor alpha) gene on chromosome 17. This fusion protein blocks the maturation of myeloid cells at the promyelocyte stage.
Answer choice A: t(8;21) translocation, is incorrect. This is a common translocation in AML (formerly M2 subtype) that involves the RUNX1-RUNX1T1 fusion. While it also features Auer rods and carries a relatively favorable prognosis, it is not as classically associated with the heavy Auer rod burden or the specific clinical risk of disseminated intravascular coagulation (DIC) seen in APL.
Answer choice B: t(9;22) translocation, is incorrect. This is the Philadelphia chromosome, the hallmark of chronic myelogenous leukemia (CML) and a poor prognostic factor in ALL. It is rare in de novo AML.
Answer choice D: t(12;21) translocation, is incorrect. This is the most common translocation in pediatric B-ALL and is associated with an excellent prognosis in children. It is not seen in AML.
Answer choice E: 11q23 rearrangement, is incorrect. This involves the KMT2A (MLL) gene and is typically associated with monocytic subtypes of AML (e.g., acute monocytic leukemia), which often present with gingival hyperplasia but lack Auer rods.
Key Learning Point
Acute Myelogenous Leukemia (AML) is a disease of older adults (median age ~65 years). The presence of Auer rods and MPO positivity are pathognomonic for myeloblasts. The t(15;17) subtype (APL) is a medical emergency because the granules in the promyelocytes can trigger disseminated intravascular coagulation (DIC). APL is uniquely treated with all-trans retinoic acid (ATRA), which forces the malignant promyelocytes to differentiate into mature neutrophils.
