Published online 10 November 2008
Haematologica, Vol 94, Issue 1, 29-37 doi:10.3324/haematol.13601
Copyright © 2009 by Ferrata Storti Foundation
Sa A. Wang1,4 ,
Olga Pozdnyakova2 ,
Jeffrey L. Jorgensen2 ,
L. Jeffrey Medeiros1 ,
Dariusz Stachurski3 ,
Mary Anderson4 ,
Azra Raza5 ,
Bruce A. Woda4
Haematologica, Vol 94, Issue 1, 29-37 doi:10.3324/haematol.13601
Copyright © 2009 by Ferrata Storti Foundation
Myelodysplastic Syndromes |
Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats
1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
2 Department of Pathology, Brigham and Women Hospital, Harvard Medical School, Boston, MA
3 Department of Pathology, Rhode Island Hospital, Brown University, Providence, RI
4 Department of Pathology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, MA
5 MDS Program, St. Vincent’s Comprehensive Cancer Center, New York, NY, USA
Correspondence: Sa A. Wang, MD, Department of Hematopathology, 1515 Holcombe Boulevard, Unit 72, Houston, TX, USA 77030-4009. E-mail:swang5{at}mdanderson.org
Background: The presence of paroxysmal nocturnal hemoglobinuria clones in the setting of aplastic anemia or myelodysplastic syndrome has been shown to have prognostic and therapeutic implications. However, the status of paroxysmal nocturnal hemoglobinuria clones in various categories of myelodysplastic syndrome and in other bone marrow disorders is not well-studied.
Design and Methods: By using multiparameter flow cytometry immunophenotypic analysis with antibodies specific for four glycosylphosphatidylinositol-anchored proteins (CD55, CD59, CD16, CD66b) and performing an aerolysin lysis confirmatory test in representative cases, we assessed the paroxysmal nocturnal hemoglobinuria-phenotype granulocytes in 110 patients with myelodysplastic syndrome, 15 with myelodysplastic/myeloproliferative disease, 5 with idiopathic myelofibrosis and 6 with acute myeloid leukemia.
Results: Paroxysmal nocturnal hemoglobinuria-phenotype granulocytes were detected in nine patients with low grade myelodysplastic syndrome who showed clinicopathological features of bone marrow failure, similar to aplastic anemia. All paroxysmal nocturnal hemoglobinuria-positive cases demonstrated loss of the four glycosylphosphatidylinositol-anchored proteins, with CD16–CD66b– clones being larger than those of CD55–CD59– (p<0.05). Altered glycosylphosphatidylinositol-anchored protein expression secondary to granulocytic hypogranulation, immaturity, and/or immunophenotypic abnormalities was present in a substantial number of cases and diagnostically challenging.
Conclusions: These results show that routine screening for paroxysmal nocturnal hemoglobinuria clones in patients with an intrinsic bone marrow disease who show no clinical evidence of hemolysis has an appreciable yield in patients with low grade myelodysplastic syndromes. The recognition of diagnostic caveats and pitfalls associated with the underlying intrinsic bone marrow disease is essential in interpreting paroxysmal nocturnal hemoglobinuria testing correctly. In our experience, the CD16/CD66b antibody combination is superior to CD55/CD59 in screening for subclinical paroxysmal nocturnal hemoglobinuria because it detects a large clone size and is less subject to analytical interference.
Key words: paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, glycosylphosphatidylinositol-anchored proteins, flow cytometry immunophenotyping, aerolysin.
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