Detection of paroxysmal nocturnal hemoglobinuria clones in patients with myelodysplastic syndromes and related bone marrow diseases, with emphasis on diagnostic pitfalls and caveats

• Published in: Haematologica (Roma) 2009-01, Vol.94 (1), p.29-37
• Main Authors: Wang, Sa A, Pozdnyakova, Olga, Jorgensen, Jeffrey L, Medeiros, L. Jeffrey, Stachurski, Dariusz, Anderson, Mary, Raza, Azra, Woda, Bruce A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anemias. Hemoglobinopathies; Biological and medical sciences; Bone Marrow Diseases - blood; Bone Marrow Diseases - classification; Bone Marrow Diseases - complications; Bone Marrow Diseases - diagnosis; CD55 Antigens - metabolism; CD59 Antigens - metabolism; Cell Differentiation; Diseases of red blood cells; Female; Hematologic and hematopoietic diseases; Hemoglobinuria, Paroxysmal - blood; Hemoglobinuria, Paroxysmal - classification; Hemoglobinuria, Paroxysmal - complications; Hemoglobinuria, Paroxysmal - diagnosis; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - classification; Myelodysplastic Syndromes - complications; Myelodysplastic Syndromes - diagnosis; Original; Phenotype
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.13601

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