BOF: Malignant (AML)

In acute promyelocytic leukaemia, the gene encoding the transcription factor RAR-alpha is fused with a number of partner genes leading to the formation of pathogenic fusion proteins. Which ONE of the following genes has NOT been described as being a partner gene in the condition?

a) MLL

b) NPM

c) NuMA

d) PLZF

e) PML

Answer:

a) MLL

Explanation

While t(15;17) with PML-RARa fusion accounts for >90% of cases of APML, a minority demonstrate translocations involving fusion partners on chromosomes 11 (PLZF and NuMA), 5 (NPM) and 17 (with an interstitial deletion, involving STAT5b). These confer variable sensitivity to all-trans-retinoic acid (ATRA) with PML-RARa, PML-NPM and PML-NuMA being relatively sensitive and PML-PLZF and PML-STAT5b resistant.

References:

Grimwade D, Biondi A, Mozziconacci M-J, et al; Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Blood 2000;96(4):1297-1308

Grimwade D, Ivey A & Huntly BJP. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood Jan 2016, 127 (1) 29-41