Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid.
All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemic (APL) blasts from patients with t(15;17) APL. However, blasts from patients with the t(11;17) variant do not differentiate in response to ATRA. Our group has identified a variant of APL characterized by t(5;17) and expression of the NPM-RAR fusion gene product. From case reports it has been difficult to establish whether ATRA induces clinical responses in patients with this variant. In order to determine whether t(5;17) blasts differentiate with ATRA, we harvested mononuclear bone marrow cells from a patient with t(5;17) APL at time of relapse and cultured them in medium containing ATRA. Morphologic analysis of cytospins after 7 days of culture revealed that 60% of cells in the ATRA-treated culture had differentiated into mature neutrophilic forms, as opposed to less than 1% in the control culture. Seventy-three percent of cells acquired NBT positivity after exposure to ATRA, compared with 1% in the control culture. These results indicate that t(5;17) blasts retain the ability to terminally differentiate in response to retinoic acid.
Redner
R L
RL
Department of Medicine, University of Pittsburgh Medical Center, University of Pittsburgh Cancer Institute, PA 15213, USA.
Corey
S J
SJ
Rush
E A
EA
D002454:Cell Differentiation / Q000187:drug effects; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin