title: Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.
abstract: All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML. We report on two patients with relapsed or refractory non-M3 AML treated with bexarotene monotherapy. After initiating treatment, both patients showed leukemic differentiation in their peripheral blood and reduction in bone marrow blasts to less than 5%. One patient had a significant improvement in her platelet count with loss of platelet transfusion needs. Differentiation syndrome occurred in one patient and was successfully treated with steroids and discontinuation of bexarotene. These data suggest that bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid differentiation in vivo.
authors.affiliation: Hematology-Oncology Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA. detsai@mail.med.upenn.edu
authors.forename: Donald E
authors.initials: DE
authors.lastname: Tsai
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.forename: Allison
authors.initials: A
authors.lastname: Kemner
authors.forename: Cezary
authors.initials: C
authors.lastname: Swider
authors.forename: Ami
authors.initials: A
authors.lastname: Goradia
authors.forename: Ewa
authors.initials: E
authors.lastname: Tomczak
authors.forename: Doris
authors.initials: D
authors.lastname: DiPatri
authors.forename: Adam
authors.initials: A
authors.lastname: Bagg
authors.forename: Peter
authors.initials: P
authors.lastname: Nowell
authors.forename: Alison W
authors.initials: AW
authors.lastname: Loren
authors.forename: Alexander
authors.initials: A
authors.lastname: Perl
authors.forename: Stephen
authors.initials: S
authors.lastname: Schuster
authors.forename: James E
authors.initials: JE
authors.lastname: Thompson
authors.forename: David
authors.initials: D
authors.lastname: Porter
authors.forename: Charlambos
authors.initials: C
authors.lastname: Andreadis
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Steven
authors.initials: S
authors.lastname: Goldsteini
authors.forename: Richard
authors.initials: R
authors.lastname: Ghalie
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
mesh_terms: D000208:Acute Disease; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077610:Bexarotene; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D047488:Retinoid X Receptors / Q000819:agonists*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene