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Rapid diagnosis of acute promyelocytic leukemia by immunohistochemical
localization of PML/RAR-alpha protein
JA Dyck, RP Warrell , RM Evans and WH Miller
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La
Jolla, CA, USA.
Acute promyelocytic leukemia (APL) is characterized by a consistent
chromosomal aberration that fuses the retinoic acid receptor alpha (RAR
alpha) gene with the novel gene PML, resulting in the expression of a
PML/RAR-alpha fusion protein. Immunohistochemical examination of APL cells
shows a unique abnormal distribution of anti-PML and anti-RAR alpha
antibody labeling. The PML labeling pattern observed in normal cells
consists of 5 to 10 discrete spherical nuclear bodies called PODs (for "PML
oncogenic domains"), whereas that of APL consists of a smaller and far more
numerous speckled pattern. We examined malignant cells from patients with a
variety of hematopoietic cancers by immunohistochemistry (IH) and found
this abnormal PML pattern expressed in cells from patients with
t(15;17)-associated leukemia but not in patients with other neoplastic
disorders. IH results agreed with reverse transcription polymerase chain
reaction for PML/RAR-alpha in 31 of 32 patients with acute myelogenous
leukemia, including 5 of 5 patients in whom the initial clinical diagnosis
of APL was not supported by cytogenetics, molecular tests, or response to
all-trans retinoic acid (RA). Cells from patients with APL were examined
during the course of retinoid therapy and at the time of complete remission
and relapse. Reorganization of the PML labeling into PODs with normal
appearance was observed in cells from patients who received RA. IH showed
primarily normal PML staining during clinical remission, although the
APL-specific labeling pattern was again seen in cells taken from patients
at the time of relapse. Thus, IH provides an independent assay for the
presence and expression of the molecular rearrangement of APL. The relative
ease and speed of detecting the APL- specific PML labeling pattern should
make IH a useful diagnostic tool to guide specific therapy of APL, and
establish a direct assay for PML/RAR-alpha protein expression and
localization in individual patient cells.
Volume 86,
Issue 3,
pp. 862-867,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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