BOF: Malignant (AML)

Which one of the following chromosomal anomalies seen in acute myeloid leukaemia is associated with the least favourable prognosis.

a) inv (16)

b) t (15;17)

c) t (5;17)

d) t (8;21)

e) t (9;11)

Answer:

The answer is:

t (9;11)

Explanation:

Cytogenetic characterisation is integral to prognostication and appropriate treatment of acute myeloid leukaemia, and contributes more than most factors to decisions regarding transplant consolidation of induction chemotherapy.

Core binding factor mutations (CBFB/MYH11: inv 16 and RUNX1/RUNX1T1 or AML1/ETO: t(8;21)) are associated with favourable prognosis, as is acute promyelocytic leukaemia with a RARA gene fusion product leading to ATRA sensitivity (usually PML-RARA: t(15;17) but occasionally NPM-RARA: t(5;17); note that other fusion products do not confer favourable prognosis).

t(9;11) or KMT2A/MLLT3 confers a poorer prognosis, although possibly superior to other translocations involving the MLL gene at 11q23, other rearrangements of which are associated with particularly poor prognosis and often monoblastic morphological phenotype.

Reference: Grimwade D, Hills RK, Moorman AV, et al; National Cancer Research Institute Adult Leukaemia Working Group. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116(3):354-365.