|
|
 Previous Article | Table of Contents | Next Article 
Immunocytochemical Diagnosis of Acute Promyelocytic Leukemia (M3) With the Monoclonal Antibody PG-M3 (Anti-PML)
Brunangelo Falini,
Leonardo Flenghi,
Marta Fagioli,
Francesco Lo Coco,
Iole Cordone,
Daniela Diverio,
Laura Pasqualucci,
Andrea Biondi,
Daniela Riganelli,
Annette Orleth,
Arcangelo Liso,
Massimo F. Martelli,
Pier-Giuseppe Pelicci, and
Stefano Pileri
From the Institutes of Hematology and Internal Medicine, University of Perugia, Perugia; Institute of Hematology, University "La Sapienza," Rome; Institute of Pediatry, Ospedale S. Gerardo, Monza; Institute of Pathology, University of Bologna, Bologna; European Institute of Oncology, Department of Experimental Oncology, Milan, Italy.
Acute promyelocytic leukemia (APL) is characterized by a reciprocal 15; 17 chromosomal translocation, which fuses the promyelocytic leukemia (PML) and retinoic acid receptor  (RAR) genes, leading to the expression of the PML/RAR fusion oncoprotein. Immunocytochemical labeling of the wild-type PML protein with the PG-M3 monoclonal antibody (MoAb) directed against the amino terminal portion of the human PML gene product, produces a characteristic nuclear speckled pattern that is due to localization of the protein into discrete dots (5 to 20 per nucleus), named PML nuclear bodies. The architecture of PML nuclear bodies appears to be disrupted in APL cells that bear the t(15; 17), thus resulting in a change of the nuclear staining pattern from speckled (wild-type PML protein) to microgranular (PML-RAR fusion protein). To assess whether the PG-M3 MoAb could assist in the diagnosis of APL (M3), bone marrow and/or peripheral blood samples from 100 cases of acute nonlymphoid leukemias of different subtypes were blindly immunostained with the PG-M3 MoAb, using the immunoalkaline phosphatase (APAAP) or immunofluorescence technique as detection system. Notably, the abnormal (micropunctate) pattern of the PML/RAR fusion protein (usually  50 small granules/per nucleus) was observed in APL (M3) samples, but not in other types of acute nonlymphoid leukemias. Immunocytochemical labeling with PG-M3 was particularly useful in the diagnosis of microgranular variant of APL (M3V) (three cases misdiagnosed as M4 and M5), and also to exclude a morphologic misdiagnosis of APL (six of 78 cases). In all cases investigated, immunocytochemical results were in agreement with those of reverse transcription-polymerase chain reaction (RT-PCR) for PML/RAR. Because the epitope identified by PG-M3 is located in the aminoterminal portion of PML (AA 37 to 51), the antibody was suitable for recognizing APL cases characterized by breakpoint occurring at different sites of PML (bcr 1, bcr 2 and bcr 3). In conclusion, immunocytochemical labeling with PG-M3 represents a rapid, sensitive, and highly-specific test for the diagnosis of APL that bears the t(15; 17). This should allow an easy and correct diagnosis of this subtype of acute leukemia to any laboratory provided with a minimal equipment for immunocytochemistry work.
Blood, Vol. 90 No. 10 (November 15), 1997:
pp. 4046-4053
© 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:
|
|
|
|
 
M. A. Sanz, D. Grimwade, M. S. Tallman, B. Lowenberg, P. Fenaux, E. H. Estey, T. Naoe, E. Lengfelder, T. Buchner, H. Dohner, et al.
Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet
Blood,
February 26, 2009;
113(9):
1875 - 1891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Vincenzi, D. Santini, G. Perrone, A. Russo, V. Adamo, S. Rizzo, F. Castri, A. Antinori, R. Alloni, P. F. Crucitti, et al.
Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients
Ann. Onc.,
January 1, 2009;
20(1):
78 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, M. P. Martelli, N. Bolli, R. Bonasso, E. Ghia, M. T. Pallotta, D. Diverio, I. Nicoletti, R. Pacini, A. Tabarrini, et al.
Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia
Blood,
September 15, 2006;
108(6):
1999 - 2005.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Condemine, Y. Takahashi, J. Zhu, F. Puvion-Dutilleul, S. Guegan, A. Janin, and H. de The
Characterization of endogenous human promyelocytic leukemia isoforms.
Cancer Res.,
June 15, 2006;
66(12):
6192 - 6198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Sanz, M. S. Tallman, and F. Lo-Coco
Practice Points, Consensus, and Controversial Issues in the Management of Patients with Newly Diagnosed Acute Promyelocytic Leukemia
Oncologist,
November 1, 2005;
10(10):
806 - 814.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Sanz, M. S. Tallman, and F. Lo-Coco
Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia
Blood,
April 15, 2005;
105(8):
3019 - 3025.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini and D. Y. Mason
Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry
Blood,
January 15, 2002;
99(2):
409 - 426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Specchia, F. Lo Coco, M. Vignetti, G. Avvisati, P. Fazi, F. Albano, F. Di Raimondo, B. Martino, F. Ferrara, C. Selleri, et al.
Extramedullary Involvement at Relapse in Acute Promyelocytic Leukemia Patients Treated or Not With All-Trans Retinoic Acid: A Report by the Gruppo Italiano Malattie Ematologiche dell'Adulto
J. Clin. Oncol.,
October 15, 2001;
19(20):
4023 - 4028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Sanz, F. L. Coco, G. Martin, G. Avvisati, C. Rayon, T. Barbui, J. Diaz-Mediavilla, G. Fioritoni, J. D. Gonzalez, V. Liso, et al.
Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups
Blood,
August 15, 2000;
96(4):
1247 - 1253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, M. Fizzotti, A. Pucciarini, B. Bigerna, T. Marafioti, M. Gambacorta, R. Pacini, C. Alunni, L. Natali-Tanci, B. Ugolini, et al.
A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells
Blood,
March 15, 2000;
95(6):
2084 - 2092.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Sanz, G. Martin, C. Rayon, J. Esteve, M. Gonzalez, J. Diaz-Mediavilla, P. Bolufer, E. Barragan, M. J. Terol, J. D. Gonzalez, et al.
A Modified AIDA Protocol With Anthracycline-Based Consolidation Results in High Antileukemic Efficacy and Reduced Toxicity in Newly Diagnosed PML/RARalpha -Positive Acute Promyelocytic Leukemia
Blood,
November 1, 1999;
94(9):
3015 - 3021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. L. Coco, D. Diverio, B. Falini, A. Biondi, C. Nervi, and P. G. Pelicci
Genetic Diagnosis and Molecular Monitoring in the Management of Acute Promyelocytic Leukemia
Blood,
July 1, 1999;
94(1):
12 - 22.
[Full Text]
[PDF]
|
|
|
|
|
