|
|
 Previous Article | Table of Contents | Next Article 
Neutrophil Secondary-Granule Deficiency as a Hallmark of All-Trans Retinoic Acid-Induced Differentiation of Acute Promyelocytic Leukemia Cells
Jun Miyauchi,
Kazuma Ohyashiki,
Yuka Inatomi, and
Keisuke Toyama
From the Division of Pathology, Clinical Laboratory, National Children's Hospital, Tokyo, Japan; and The First Department of Internal Medicine, Tokyo Medical College, Tokyo, Japan.
Acute promyelocytic leukemia (APL) is a neoplasm with the unique chromosomal translocation t(15; 17), which involves the retinoic acid receptor  gene. All-trans retinoic acid (ATRA) has been used for APL patients as a potent therapeutic agent to induce differentiation of leukemia cells. Although polymorphonuclear leukocytes (PMNs) appearing in the blood and bone marrow during ATRA treatment often possess Auer rods, indicating their neoplastic origin, other morphological abnormalities of PMNs have not been elucidated. We studied the morphological changes of APL cells during ATRA treatment at the ultrastructural level. Although most aberrant primary granules, including Auer rods, became morphologically normal in response to ATRA therapy and the nuclei showed chromatin condensation and lobulation, resulting in the emergence of PMNs, the lobulated nuclei often had nuclear filamentous connections and/or nuclear blebs, indicating some pathological process. Furthermore, PMNs, particularly early in ATRA treatment, lacked neutrophil secondary granules as did the PMNs appearing in a culture of APL cells incubated with ATRA, findings consistent with previously reported data that acute myeloid leukemia cell lines do not produce secondary granule proteins even after induction of differentiation towards mature neutrophils. The present data indicate that ATRA is incapable of inducing complete morphological maturation of APL cells and that secondary-granule deficiency may be a hallmark of aberrantly differentiated leukemic cells.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 803-813
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Lukasova, Z. Koristek, M. Falk, S. Kozubek, S. Grigoryev, M. Kozubek, V. Ondrej, and I. Kroupova
Methylation of histones in myeloid leukemias as a potential marker of granulocyte abnormalities
J. Leukoc. Biol.,
January 1, 2005;
77(1):
100 - 111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. C. Guibal, C. Moog-Lutz, P. Smolewski, Y. Di Gioia, Z. Darzynkiewicz, P. G. Lutz, and Y. E. Cayre
ASB-2 Inhibits Growth and Promotes Commitment in Myeloid Leukemia Cells
J. Biol. Chem.,
January 4, 2002;
277(1):
218 - 224.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Melnick and J. D. Licht
Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia
Blood,
May 15, 1999;
93(10):
3167 - 3215.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Labrecque, D. Allan, P. Chambon, N. N. Iscove, D. Lohnes, and T. Hoang
Impaired Granulocytic Differentiation In Vitro in Hematopoietic Cells Lacking Retinoic Acid Receptors alpha 1 and gamma
Blood,
July 15, 1998;
92(2):
607 - 615.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
