Pathology · Hematological Malignancies (Leukemias, Lymphomas, Myeloma)

A 65-year-old man with chronic lymphocytic leukaemia (CLL) is found to have del(17p13) on FISH. This deletion targets TP53 and predicts all of the following EXCEPT:

  • A Resistance to fludarabine-based chemoimmunotherapy
  • B Shortened overall survival compared to CLL without del(17p)
  • C Poor response to ibrutinib (BTK inhibitor)
  • D Requirement for upfront targeted therapy rather than watch-and-wait for asymptomatic patients
Correct answer: C. Poor response to ibrutinib (BTK inhibitor)

Explanation

Del(17p13)/TP53 deletion in CLL renders it highly resistant to conventional chemotherapy (fludarabine, bendamustine, chlorambucil) because DNA-damaging drugs require intact p53 to trigger apoptosis. Overall survival is markedly shortened compared to IGHV-mutated CLL without this deletion. However, ibrutinib (BTK inhibitor) and venetoclax (BCL-2 inhibitor) act via p53-independent pathways and retain efficacy in del(17p) CLL — these are now the preferred agents. Asymptomatic patients with del(17p) are typically observed until they require treatment; the deletion itself (without symptoms/organomegaly/cytopenias) does not mandate upfront therapy.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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