Probing the pathobiology of response to all-trans retinoic acid in acute
promyelocytic leukemia: premature chromosome condensation/fluorescence in
situ hybridization analysis
RC Vyas, SR Frankel, P Agbor, WH Miller , RP Warrell and WN Hittelman
Department of Clinical Investigation, University of Texas M.D. Anderson
Cancer Center, Houston, USA.
The response of acute promyelocytic leukemia (APL) peripheral blood and
bone marrow cells to trans-retinoic acid (RA) was cytogenetically
characterized during RA treatment using the techniques of premature
chromosome condensation (PCC) and fluorescence in situ hybridization
(FISH). Before treatment, the predominant immature bone marrow cells were
found to have t(15;17), whereas the residual mature granulocytes were
diploid and lacked evidence of the translocation. In response to RA
treatment, an increase in the leukocyte count was noted. The majority of
these cells exhibited a t(15;17). Subsequently (eg, between days 6 and 23),
32% to 91% of the maturing myeloid cells still exhibited t(15;17). The
appearance of t(15;17) in gradually maturing elements suggests that RA
contributed to a release of the maturation block of the leukemic elements.
As responding patients obtained complete remission, diploid elements
without evidence of the translocation prevailed in the blood and bone
marrow. In 16 patients studied after 1 month in complete remission, all but
2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days
later in 1 patient, whereas the second patient exhibited clinical evidence
of relapse 20 days later. These results suggest that response of patients
with APL to RA is associated with maturation, subsequent loss of the mature
leukemic elements, and preferential regeneration of normal diploid
hematopoietic elements.
Volume 87,
Issue 1,
pp. 218-226,
01/01/1996
Copyright © 1996 by The American Society of Hematology
