A 5-year-old child is diagnosed with B-cell precursor ALL. Cytogenetics reveal t(9;22) (Philadelphia chromosome). This translocation specifically affects prognosis because:
- A It confers resistance to L-asparaginase, the backbone of ALL therapy
- B It predicts superior response to high-dose methotrexate
- C It is associated with a BCR-ABL1 fusion protein with constitutive tyrosine kinase activity, conferring poor prognosis unless tyrosine kinase inhibitor is added ✓
- D It occurs only in TEL-AML1-negative cases with good prognosis
Correct answer: C. It is associated with a BCR-ABL1 fusion protein with constitutive tyrosine kinase activity, conferring poor prognosis unless tyrosine kinase inhibitor is added
Explanation
t(9;22)(q34;q11) in childhood ALL generates BCR-ABL1 fusion (p190 isoform predominantly in ALL), encoding a constitutively active tyrosine kinase that drives leukemic proliferation and confers poor prognosis with standard chemotherapy. Addition of imatinib (or dasatinib) dramatically improves outcomes. Ph+ ALL historically had <30% EFS with chemotherapy alone; this figure rises above 60–70% with TKI addition. TEL-AML1 (t(12;21)) is a good-prognosis translocation, not related to Ph+.
Reference: Ghai Essential Pediatrics, 10th ed.
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