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

Khoury, Haytham; Dalal, Bakul I.; Nantel, Stephen H.; Horsman, Douglas E.; Lavoie, Julye C.; Shepherd, John; Hogge, Donna E.; Toze, Cynthia L.; Song, Kevin; Forrest, Donna L.; Sutherland, Heather J.; Nevill, Thomas J.

doi:10.1038/modpathol.3800168

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…In accordance with a previous report, 55 we observed low CD33 expression levels in blasts of patients with t(8;21). Another recent study reported higher CD33 expression in AMLs with NPM1 mutation, 56 which is confirmed by our findings.…”

Section: Discussionsupporting

confidence: 93%

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

Ehninger

Kramer

Röllig

et al. 2014

Blood Cancer Journal

273

208

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Owing to the more recent positive results with the anti-CD33 immunotoxin gemtuzumab ozogamicin, therapy against acute myeloid leukemias (AMLs) targeting CD33 holds many promises. Here, CD33 and CD123 expression on AML blasts was studied by flow cytometry in a cohort of 319 patients with detailed information on French–American–British/World Health Organization (FAB/WHO) classification, cytogenetics and molecular aberrations. AMLs of 87.8% express CD33 and would therefore be targetable with anti-CD33 therapies. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. Thus, nearly all AMLs could be either targeted via CD33 or CD123. Simultaneous presence of both antigens was observed in 69.5% of patients. Most importantly, even AMLs with adverse cytogenetics express CD33 and CD123 levels comparable to those with favorable and intermediate subtypes. Some patient groups with unfavorable alterations, such as FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations, high FLT3-ITD mutant/wild-type ratios and monosomy 5 are even characterized by high expression of CD33 and CD123. In addition, blasts of patients with mutant nucleophosmin (NPM1) revealed significantly higher CD33 and CD123 expression pointing toward the possibility of minimal residual disease-guided interventions in mutated NPM1-positive AMLs. These results stimulate the development of novel concepts to redirect immune effector cells toward CD33- and CD123-expressing blasts using bi-specific antibodies or engineered T cells expressing chimeric antigen receptors.

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Section: Discussionsupporting

confidence: 93%

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

Ehninger

Kramer

Röllig

et al. 2014

Blood Cancer Journal

273

208

View full text Add to dashboard Cite

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“…A previous study reported that CD34 was expressed in 62% of non-APL and 17% of APL (all microgranular variants) cases [17]. In the present study, CD34 expression was significantly less frequent in APL cases than in non-APL.…”

Section: Disussionmentioning

confidence: 32%

“…Furthermore, HLA-DR negative non-APL showed a lower incidence of CD34 expression than did Another study also demonstrated that the incidence of CD34 expression was higher in HLA-DR positive non-APL (79%) than in HLA-DR negative non-APL patients (17%) [18]. Especially, 10% of non-APL patients were negative for both CD34 and HLA-DR [17]. One author reported that invaginated nuclear morphology was associated with loss of HLA-DR and CD34 expressions in non-APL [19].…”

Section: Disussionmentioning

confidence: 83%

Characteristics of Acute Myeloid Leukemia without HLA-DR Expression

et al. 2007

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Immunophenotype is one of the most useful tool for the identification of leukemia subtypes [1][2][3][4][5] and can be assigned within a few hours after bone marrow sampling.The typical immunophenotypic feature of acute promyelocytic leukemia (APL) has been reported as CD34-, HLA-DR-, CD13+, and CD33+ [6][7][8]. It has been reported that HLA-DR antigens are consistently negative in APL, whereas the majority of non-APL cases are positive for HLA-DR expression [9,10]; therefore, HLA-DR negativity is known to be useful for distinguishing APL from other AML subtypes, even before the PML-RARA gene rearrangement is identified by cytogenetic or molecular stud- Background : 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.Methods : 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.Results : 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.Conclusions : 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. (Korean J Lab Med 2007;27:313-7)

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“…This protein, AML1-ETO, act as a negative dominant inhibitor of wild-type AML1 [27], which theoretically could lead to down-regulation of AML1 target genes, such as MPO gene. However, blasts with t(8;21) have been shown to display higher levels of MPO expression both in clinical samples and in vitro experiments [28,29], CEBPA mutations are associated with a relatively favorable outcome, and it was recently shown in a multivariable analysis including cytogenetic risk and the FLT3-ITD and NPM1 mutations that the CEBPA double-mut genotype is associated with favorable overall and event-free survival [15][16]. In a cohort of 60 cases of adult de novo AML, we identified 1 CEBPA single-mut case and 10 CEBPA double-mut cases, and in line with previous reports, our study tended to show better overall survival in CEBPA double-mut cases compared to cases with wild-type CEBPA in patients treated with intensive chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts

et al. 2011

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The percentage of myeloperoxidase (MPO)-positive blast cells is a simple and highly significant prognostic factor in AML patients. It has been reported that the high MPO group (MPO-H), in which >50% of blasts are MPO activity positive, is associated with favorable karyotypes, while the low MPO group (≤50% of blasts are MPO activity positive, MPO-L) is associated with adverse karyotypes. The MPO-H group shows better survival even when restricted to patients belonging to the intermediate chromosomal risk group or those with a normal karyotype. It has recently been shown that genotypes defined by the mutational status of NPM1, FLT3, and CEBPA are associated with treatment outcome in patients with cytogenetically normal AML. In this study, we aimed to evaluate the relationship between MPO positivity and gene mutations found in normal karyotypes. Sixty AML patients with normal karyotypes were included in this study. Blast cell MPO positivity was assessed in bone marrow smears stained for MPO. Associated genetic lesions (the NPM1, FLT3-ITD, and CEBPA mutations) were studied using nucleotide sequencing. Thirty-two patients were in the MPO-L group, and 28 patients in the MPO-H group. FLT3-ITD was found in 11 patients (18.3%), NPM1 mutations were found in 19 patients (31.7%), and CEBPA mutations were found in 11 patients (18.3%). In patients with CEBPA mutations, the carrying two simultaneous mutations (CEBPA double-mut ) was associated with high MPO expression, while the mutant NPM1 without FLT3-ITD genotype was not associated with MPO activity. Both higher MPO expression and the CEBPA double-mut genotype appeared to be associated with improved overall survival after intensive chemotherapy. Further studies are required to determine the importance of blast MPO activity as a prognostic factor, especially in CEBPA wild-type patients with a normal karyotype.

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

Cited by 18 publications

References 27 publications

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia

Characteristics of Acute Myeloid Leukemia without HLA-DR Expression

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts

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