Title : Missense mutations in the PML/RARalpha ligand binding domain in ATRA-resistant As(2)O(3) sensitive relapsed acute promyelocytic leukemia.

Pub. Date : 1999 Nov

PMID : 10553155






4 Functional Relationships(s)
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1 All-trans retinoic acid probably induces differentiation of atypical promyelocytes and clinical remission in APL patients by binding to the ligand binding domain (LBD) of the RARa portion of the PML-RARa chimeric protein. Tretinoin PML nuclear body scaffold Homo sapiens
2 Structural alterations of the LBD of the PML/RARa have been revealed in ATRA-resistant APL cell lines and in a few APL patients with acquired clinical resistance to ATRA therapy. Tretinoin PML nuclear body scaffold Homo sapiens
3 Two APL relapsed patients with clinical resistance to ATRA therapy were evaluated for the presence of nucleotide mutations in the LBD of PML/RARa gene and then treated with arsenic trioxide (As2O3). Tretinoin PML nuclear body scaffold Homo sapiens
4 RESULTS: In both patients, at the ATRA-resistant relapse, a missense point mutation in the LBD of the PML/RARa gene was found. Tretinoin PML nuclear body scaffold Homo sapiens