Flow cytometric analysis of myelomonocytic cells by a pattern recognition approach is sensitive and specific in diagnosing myelodysplastic syndrome and related marrow diseases: Emphasis on a global evaluation and recognition of diagnostic pitfalls

Stachurski, Dariusz; Smith, Brian R.; Pozdnyakova, Olga; Andersen, Mary; Xiao, Zhiqing; Raza, Azra; Woda, Bruce A.; Wang, Sa A.

doi:10.1016/j.leukres.2007.06.012

Cited by 81 publications

(98 citation statements)

References 25 publications

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“…By applying the principles of information geometry in the current study, we corroborated observations that have been made in previous studies involving subjective interpretation of myeloid immunophenotypes, including substantial overlap in the immunophenotypic signatures between benign granulopoiesis and the granulopoiesis of low grade MDS and the tendency of higher grade MDS (RAEB and RCMD) to separate immunophenotypically from benign cases (5,6,15). This finding was further validated by the observation that MDS cases with morphologic dysgranulopoiesis showed greater separation from benign cases than did MDS cases without morphologic dysgranulopoiesis.…”

Section: Discussionsupporting

confidence: 87%

“…Documentation of abnormal, imbalanced, or dyssynchronous myeloid maturation patterns has been a key focus of most studies on the use of flow cytometric immunophenotyping in the diagnosis of MDS (2)(3)(4)(5)(13)(14)(15). This type of analysis generally has a substantial subjective component, requiring an individual user to weigh qualitatively the expression patterns among several markers, to weigh the importance of maturational shifts or myeloblast increases, and to render conclusions regarding the sometimes subtle deviations and between observed and expected patterns yielded by these marker combinations on examination of serial 2D histograms.…”

Section: Discussionmentioning

confidence: 99%

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Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

Finn

Harrington

Carter

et al. 2011

Cytometry Part B Clinical

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Background: The role of flow cytometry (FCM) in diagnosing myelodysplastic syndromes (MDS)remains controversial, because analysis of myeloid maturation may involve subjective interpretation of sometimes subtle patterns on multiparameter FCM.Methods: Using six-parameter marker combinations known to be useful in evaluating the myeloid compartment in MDS, we measured objective immunophenotypic differences between non-neoplastic (n 5 25) and dysplastic (n 5 17) granulopoiesis using a novel method, called Fisher information nonparametric embedding (FINE), that measures information distances among FCM datasets modeled as individual high-dimensional probability density functions, rather than as sets of two-dimensional histograms. Information-preserving component analysis (IPCA) was used to create information-optimized ''rotated'' twodimensional histograms for visualizing myelopoietic immunophenotypes for each individual sample.Results: There was a consistent trend of segregation of higher-grade MDS (RAEB and RCMD) from benign by FINE analysis. This difference was accentuated in cases with morphologic dysgranulopoiesis and in cases with clonal cytogenetic abnormalities. However, lower grades of MDS or cases that lacked morphologic dysgranulopoiesis showed much greater overlap with non-neoplastic cases. Two cases of reactive left shift were consistently embedded within the higher-grade MDS group. IPCA yielded twodimensional histogram projections for each individual case by relative weighting of measured cellular characteristics, optimized for preserving information distances derived through FINE.Conclusions: Objective analysis by information geometry supports the conclusions of previous studies that there are immunophenotypic differences in the maturation patterns of benign granulopoiesis and high grade MDS, but also reinforces the known pitfalls of overlap between low-grade MDS and benign granulopoiesis and overlap between reactive granulocytic left shifts and dysplastic granulopoiesis.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

Finn

Harrington

Carter

et al. 2011

Cytometry Part B Clinical

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“…This problem may be further complicated by decreased CD15 expression on granulocytes and substantially increased CD15 expression on mononcytes, an alteration often observed in MDS bone marrow cells. 22 Although our stringent three-step gating strategy showed greater utility in separating granulocytes from monocytes as compared to the CD15/SSC and FSC/SSC two-step gating recommended by others, 8 in some cases, especially the cases with severe granulocytic dysplasia and/or CMML, a small number of monocytes were inseparable from granulocytes and were included in the granulocyte gate. Monocytes have a CD16 -CD66b -immunophenotype and can be mistaken for cells with a PNH + phenotype.…”

Section: Cd66bmentioning

confidence: 85%

“…22 In brief, the bone marrow samples were analyzed for aberrant antigenic expression or altered expression in blasts, differentiating myeloid cells and monocytes according to our previously published protocol and analytic approaches. 22 The FCM results were correlated with the morphological and cytogenetic findings to render a final diagnosis and disease classification. In cases of AML, expression of myeloperoxidase, Tdt, cytoplasmic CD22, and cytoplasmic CD3 was assessed.…”

Section: Bone Marrow Samplesmentioning

confidence: 99%

“…22,[26][27][28] It is also known that the peripheral blood of MDS patients often contains hypogranular neutrophils and/or immature myeloid cells. Although the immunophenotypic aberrancies in myeloid cells may be less pronounced in the peripheral blood than in the bone marrow, Cheiran et al 29,30 were able to demonstrate significant immunophenotypic alterations in MDS peripheral blood granulocytes, as compared to healthy controls.…”

Section: Cd66bmentioning

confidence: 99%

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

Wang¹,

Pozdnyakova

Jorgensen³

et al. 2009

Haematologica

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BackgroundThe 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 MethodsBy 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. ResultsParoxysmal 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. ConclusionsThese 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.

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Myelodysplastic Syndromes and Myeloproliferative Neoplasms

Leach

Drummond

Doig

2013

Practical Flow Cytometry in Haematology Diagnosis

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Flow cytometric analysis of myelomonocytic cells by a pattern recognition approach is sensitive and specific in diagnosing myelodysplastic syndrome and related marrow diseases: Emphasis on a global evaluation and recognition of diagnostic pitfalls

Cited by 81 publications

References 25 publications

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

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

Myelodysplastic Syndromes and Myeloproliferative Neoplasms

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