Acute Myelogenous Leukemia with t(8;21)—Identification of a Specific Immunophenotype

Khoury, Haytham; Dalal, Bakul I.; Nevill, Thomas J.; Horsman, Douglas E.; Barnett, Michael J.; Shepherd, John; Toze, Cynthia L.; Conneally, Eibhlin; Sutherland, Heather J.; Hogge, Donna E.; Nantel, Stephen H.

doi:10.1080/1042819031000116698

Cited by 46 publications

(24 citation statements)

References 25 publications

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“…[11][12][13] We have shown that combined CD34, CD19 and CD56 positivity in AML patients has a 67% sensitivity, 100% specificity and a positive predictive value of 100% for the presence of t(8;21). 14 Despite support for the existence of a unique immunophenotype in AML with t(8;21), quantitative immunophenotyping in this form of AML has rarely been reported. 13 Recent reports have suggested that quantitative immunophenotyping may enhance the diagnosis of leukemias with specific cytogenetic abnormalities [15][16][17] and help define aberrant immunophenotyping patterns that could be useful for monitoring minimal residual disease.…”

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confidence: 99%

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

et al. 2004

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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 (Po0.001 for each) and lower levels of CD13 (P ¼ 0.03) and CD33 (P ¼ 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 (CD34460.5 Â 10 3 , HLA-DR4176.1 Â 10 3 , MPO4735.1 Â 10 3 , CD13o24.3 Â 10 3 and CD33o17.3 Â 10 3 ) had a sensitivity of 100%, a specificity of 62-92% and a positive predictive value of 7-45%. In multivariate analysis, two quantitative patterns (CD34460.5 Â 10 3 and MPO4176.1 Â 10 3 ; CD33o17.3 Â 10 3 and MPO4176.1 Â 10 3 ) 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. In patients with acute myelogenous leukemia (AML), t(8;21)(q22;q22) is a relatively frequent structural cytogenetic abnormality. This chromosomal translocation results in an in-frame fusion between the first 5 exons of the AML1 gene and essentially all of the ETO gene producing a chimeric protein. 1 This protein, AML1-ETO, retains the ability of AML1 to heterodimerize with CBFb and to bind DNA as well as allowing ETO to interact with the N-Co-R/Sin3/HDAC complex. 2 This results in its acting as a negative dominant inhibitor of wild-type AML1. 3 The creation of AML1-ETO is necessary, but not sufficient, for leukemogenesis in AML with t(8;21). 4 The recently developed WHO classification of hematologic malignancies recognizes AML with t(8;21) as a distinct clinicopathologic entity. 5 This form of AML is found more frequently in children and young adults 6 and patients are predisposed to extramedullary localization. 7 Complete remission rates and long-term event-free survival are high, particularly when treatment incorporates high-dose cytosine arabinoside. 8 Histopathology characteristically demonstrates frequent type III

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

et al. 2004

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“…In AML, characteristic antigens have been related to particular morphological FAB subtypes and associated with the presence of recurrent genetic abnormalities (Bagg, 2007), such as AML-M2 with t(8;21) that shows aberrant expression of lymphoid markers include CD19 and CD56 (Khoury et al, 2003), another one is coexpression of CD2 in M4E with inv(16) or t(16; 16), although not specific for this type of AML (Dunphy, 1999;Medeiros et al, 2010) and M5 with t(9;11) is reported to have high expression CD56 (Graf et al, 2005;Wang et al, 2005). Regarding ALL, t (9; 22) was reported to be more frequently observed in My+B ALL than in My-B ALL (Wu et al, 2007).…”

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confidence: 99%

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia: A Retrospective Cohort Study in Makah Al Mukaramah, Saudi Arabia

Abdulateef

Ismail²,

Aljedani³

2014

Asian Pacific Journal of Cancer Prevention

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“…In all reported AML patients with t(7;21)(p22;q22) including our current case, the common features in these patients include: 1) Aberrant CD56 expression (8/9 patients) and aberrant CD7 expression (6/9 patients). No patients had expression of CD19, which is commonly seen in t(8;21) [13,14]. 2) Myelomonocytic or monocytic differentiation was common (6/9), and 3/9 patients did not show maturation or showed minimal differentiation.…”

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confidence: 99%

Acute myeloid leukemia with t(7;21)(p22;q22) and 5q deletion: a case report and literature review

Loo

Pullarkat

et al. 2014

Exp Hematol Oncol

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The gene RUNX1 at chromosome 21q22 encodes the alpha subunit of Core binding factor (CBF), a heterodimeric transcription factor involved in the development of normal hematopoiesis. Translocations of RUNX1 are seen in several types of leukemia with at least 21 identified partner genes. The cryptic t(7;21)(p22;q22) rearrangement involving the USP42 gene appears to be a specific and recurrent cytogenetic abnormality. Eight of the 9 cases identified in the literature with this translocation were associated with acute myeloid leukemia (AML), with the remaining case showing refractory anemia with excess blasts, type 2. Herein, we present a patient with two preceding years of leukopenia and one year of anemia prior to the diagnosis of AML, NOS with monocytic differentiation (myelomonocytic leukemia) whose conventional cytogenetics showed an abnormal clone with 5q deletion. Interphase FISH using LSI RUNX1/RUNXT1 showed three signals for RUNX1. FISH studies on previously G-banded metaphases showed the extra RUNX1 signal on the short arm of chromosome 7. Further characterization using the subtelomeric 7p probe showed a cryptic 7;21 translocation. Our case and eight previously reported leukemic cases with the t(7;21)(p22;q22) appear to share similar features including monocytic differentiation, immunophenotypic aberrancies (often with CD56 and/or CD7), and a generally poor response to standard induction chemotherapy. About 80% of these cases had loss of 5q material as an additional abnormality at initial diagnosis or relapse. These findings suggest that t(7;21) may represent a distinct recurrent cytogenetic abnormality associated with AML. The association between the t(7;21) and 5q aberrancies appears to be non-random, however the pathogenetic connection remains unclear. Additional studies to evaluate for RUNX1 partner genes may be considered for AML patients with RUNX1 rearrangement and 5q abnormalities; however knowledge of the prognostic implications of this rearrangement is still limited.

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Acute Myelogenous Leukemia with t(8;21)—Identification of a Specific Immunophenotype

Cited by 46 publications

References 25 publications

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

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

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia: A Retrospective Cohort Study in Makah Al Mukaramah, Saudi Arabia

Acute myeloid leukemia with t(7;21)(p22;q22) and 5q deletion: a case report and literature review

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