Correlation between karyotype and quantitative immunophenotype in acute myelogenous leukemia with t(8;21)

Department of Cellular and Molecular Biology, Princess Margaret Hospital, Toronto, Ontario, Canada.
Modern Pathology (Impact Factor: 6.19). 06/2004; 17(10):1211-1216. DOI: 10.1038/modpathol.3800168


Acute myelogenous leukemia with t(8;21) is a distinct clinicopathologic entity in which the malignant myeloblasts display a characteristic pattern of surface antigen expression. Quantitative analysis of surface marker expression in patients with this chromosomal abnormality compared to acute myelogenous leukemia patients with a different karyotype has not been reported. From 305 consecutive newly diagnosed acute myelogenous leukemia patients underwent immunophenotyping and cytogenetic analysis at our center; 16 patients (5.2%) had a t(8;21). Fluorescence intensity values were obtained, using a set of reference microbeads, by conversion of mean channel fluorescence to molecular equivalent of soluble fluorochrome. Patients with t(8;21) displayed higher levels of CD34, HLA-DR and MPO expression (P<0.001 for each) and lower levels of CD13 (P=0.03) and CD33 (P=0.02) expression. In order to study the sensitivity, specificity and predictive value of these markers, molecular equivalent of soluble fluorochrome thresholds were statistically determined. The statistically established threshold for each of the individual markers (CD34>60.5 103, HLA-DR>176.1 103, MPO>735.1 103, CD13<24.3 103 and CD33<17.3 103) had a sensitivity of 100%, a specificity of 62–92% and a positive predictive value of 7–45%. In multivariate analysis, two quantitative patterns (CD34>60.5 103 and MPO>176.1 103; CD33<17.3 103 and MPO>176.1 103) had a sensitivity, specificity and positive predictive value of 100%. These aberrant phenotypic patterns might help identify patients with t(8;21) at diagnosis and could be useful in minimal residual disease monitoring.Keywords: AML, t(8;21), quantitative immunophenotype

Download full-text


Available from: Bakul Dalal, Aug 14, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The blasts of acute myeloid leukemia (AML) with t(8;21)(q22;q22) frequently express the B-cell antigen CD19, which is regulated by B cell-specific activator protein (BSAP) encoded by the PAX5 gene, a protein important for B-cell lineage commitment and development. We assessed for BSAP expression in 28 AML cases with t(8;21) and 46 AML cases of other types. CD19 was expressed by 26 (93%) cases of AML with t(8;21) and 1 AML case (2%) without t(8;21). We also tested a subset of cases for the B-cell transcription factors Oct2 and OCA-B (BOB.1) and the B-cell antigens CD20, CD22, and CD79a. Immunostaining performed on bone marrow biopsy specimens demonstrated BSAP expression in all 28 AML cases with t(8;21): weak, 21; strong, 7. By contrast, BSAP was expressed weakly in only 1 AML case without t(8;21). Oct2 was expressed strongly in 12 of 16 AML cases with t(8;21) and 19 of 46 without t(8;21). OCA-B, CD20, CD22, or CD79a were negative in all cases assessed. These results indicate that silencing of PAX5 is not required for commitment to myeloid differentiation and that BSAP expression in AML is found mainly in cases with t(8;21).
    American Journal of Clinical Pathology 09/2006; 126(2):235-40. DOI:10.1309/LG0Q-0VXY-BETJ-4VHE · 2.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Flow cytometry is semi-automated study of antigen profile of cells using the Scatchard principle of antigen-antibody binding and fluorochrome-based detection systems. Flow cytometric evaluation of cellular proteomics has become an integral part of the laboratory diagnosis and classification of haematopoietic neoplasms. Recent technical advances in lasers, monoclonal antibodies, fluorochromes, and computer-based color compensation algorithms have expanded the usefulness of flow cytometry. Detection of minimal residual disease by flow cytometry in leukaemias and lymphomas is incorporated in many treatment protocols. Finding of aberrant maturation pattern of granulocytes offers a sensitive screening tool for early diagnosis of myelodysplastic syndromes. Detailed proteomic analysis of leukemias is helping more precise prognostic and biological stratification.
    The Journal of the Association of Physicians of India 09/2007; 55:571-3.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HLA-DR negativity is known to be useful for distinguishing acute promyelocytic leukemia (APL) from other subtypes of AML, but non-APL cases without HLA-DR antigen expression have been reported. The purpose of this study was to evaluate and compare the characteristics of APL, HLA-DR negative non-APL, and HLA-DR positive non-APL cases. A total of 114 cases of AML admitted at Ewha Womans University, Mokdong Hospital between March 1997 and June 2006 were included in this study. A diagnosis of AML was made based on the results of morphology, cytochemistry, immunophenotype, cytogenetics, and/or fluorescence in situ hybridization. Among the 114 AML patients, HLA-DR antigen was not expressed in 39 (34%), including 24 non-APL (62%) and 15 APL patients (38%). The HLA-DR negative non-APL group showed higher leukocyte counts and positive rate of CD19 expression than did APL group (P<0.05). The remaining laboratory findings were not statistically different between the HLA-DR negative non-APL and APL groups. CD34 expression was more frequent in the HLA-DR positive non-APL group than in the HLA-DR negative non-APL group and APL group. Of the 24 patients with HLA-DR negative non-APL, 7 patients had disseminated intravascular coagulation and 2 patients showed morphologic features similar to those of APL. CD19 expression and leukocyte count may be helpful for differentiating HLA-DR negative non-APL from APL. However, the final diagnosis and classification should be confirmed by cytogenetic or molecular studies.
    The Korean Journal of Laboratory Medicine 10/2007; 27(5):313-7. DOI:10.3343/kjlm.2007.27.5.313 · 1.31 Impact Factor
Show more