A 4-year-old boy presents with a 3-week history of pallor, fatigue, and petechiae. CBC reveals pancytopenia with 35% circulating blasts. Bone marrow aspirate shows 60% lymphoblasts with immunophenotype CD19+ CD10+ CD22+ TdT+ surface Ig-negative. Cytogenetic analysis by G-banding appears normal, but FISH reveals the translocation marked **A** in the diagram. Which of the following best describes the clinical and prognostic significance of this finding?
A. It is the most common translocation in infant ALL and is associated with KMT2A-rearrangement, requiring intensified chemotherapy from induction
B. It is the most frequent recurrent cytogenetic abnormality in pediatric B-ALL (~20-25% of cases) and is associated with favorable risk and >90% 5-year event-free survival
C. It is visible on G-banding in >80% of pediatric B-ALL cases and indicates a need for immediate stem cell transplantation in first remission
D. It is cryptic on standard karyotyping and requires FISH or RT-PCR for detection; it is associated with adverse prognosis and early relapse in most patients
Explanation
Why option 1 is correct
The translocation marked A, t(12;21)(p13;q22) ETV6-RUNX1 (formerly TEL-AML1), is the single most frequent recurrent cytogenetic abnormality in pediatric B-cell precursor acute lymphoblastic leukemia, occurring in approximately 20–25% of cases. This translocation is a favorable-risk marker with excellent prognosis: 5-year event-free survival exceeds 90%, particularly when minimal residual disease (MRD) is negative at the end of induction. The fusion oncoprotein impairs normal hematopoietic differentiation; the initial in-utero translocation creates a pre-leukemic clone, and additional somatic hits (commonly deletion of the residual ETV6 allele) drive overt leukemia in childhood, with peak incidence at 2–6 years of age. This patient's clinical presentation (age 4, insidious onset, pancytopenia with blasts, CD19+ CD10+ immunophenotype) and FISH-detected ETV6-RUNX1 fusion are entirely consistent with this favorable-risk subtype.
Why each distractor is wrong
Option 2: While it is true that t(12;21) is cryptic on standard G-banding and requires FISH or RT-PCR for detection, the second part is incorrect. ETV6-RUNX1 is associated with favorable prognosis, not adverse prognosis or early relapse. Adverse markers include BCR-ABL1, KMT2A-rearrangement, hypodiploidy, and iAMP21.
Option 3: The t(12;21) translocation is not visible on G-banding in the majority of cases; it is cryptic and requires molecular methods for detection. Furthermore, ETV6-RUNX1-positive patients do not routinely require stem cell transplantation in first remission because of their favorable risk profile and excellent response to multi-agent chemotherapy.
Option 4: The t(12;21) ETV6-RUNX1 fusion is not the most common translocation in infant ALL. Infants with ALL are more commonly characterized by KMT2A (formerly MLL) rearrangements, which carry an adverse prognosis. The peak incidence of ETV6-RUNX1 ALL is 2–6 years, not infancy.
High-YieldNEET PG
t(12;21) ETV6-RUNX1 is the most common recurrent cytogenetic abnormality in pediatric B-ALL (~20–25%), is cryptic on G-banding, and is a favorable-risk marker with >90% 5-year EFS.
Robbins Basic Pathology 11e; COG ALL Risk Stratification
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