The immunophenotype of acute myeloid leukemia: is there a relationship with prognosis?

doi:10.1016/j.blre.2005.08.002

Blood Reviews

Volume 20, Issue 2, March 2006, Pages 71-82

https://doi.org/10.1016/j.blre.2005.08.002 Get rights and content

Summary

Immunophenotyping of acute myeloid leukemia has controversial implications with regards to prognosis. Many associations have been described between individual antigen expression on myeloid blasts and prognosis, however few are consistent. Markers with a consistent prognostic association that have been demonstrated in more than one study have been CD13, CD14, and CD15. The association of the expression of CD11b with poor prognosis appears definite, as does CD7 expression. When compared with the expression of a single antigen, a pattern of antigen expression is likely to have a more significant relationship to prognosis. This is exemplified by the panmyeloid phenotype (expression of 5 myeloid antigens) which appears to be associated with a good prognosis and may differentiate a subgroup within an otherwise intermediate prognosis group of patients. Further analysis with the inclusion of novel antibodies and the combination of multiple antibodies to create further subgroups such as the panmyeloid phenotype will continue to enhance knowledge in this area.

Introduction

The immunophenotyping of blasts in bone marrow and peripheral blood samples from patients at diagnosis with acute myeloid leukemia (AML) is current standard practice. The findings from these investigations are used to complement morphology, cytochemistry, cytogenetic and molecular studies to determine diagnosis and predict prognosis.1, 2, 3 Leukemic myeloblasts are characterized by the expression of a variety of leukocyte differentiation antigens. These are associated with commitment to the myeloid lineage of differentiation and with the level of maturation. In addition, the expression of markers not normally associated with myeloid lineage is found in a proportion of patients and may be used for both diagnosis and detection of minimal residual disease, for example, the expression of CD19 in AML associated with t(8;21).

The diagnostic value of immunophenotyping in adult AML is clear, particularly in the differentiation of AML from lymphoid leukemias. Immunophenotyping is of particular value in ambiguous lineage or biphenotypic leukemia. It is also a valuable tool for the detection of minimal residual disease (MRD) in the majority of cases of AML.⁴ However, the prognostic value of the immunophenotype of myeloblasts in adult AML is still the subject of some debate without a definitive resolution.

The markers with significant prognostic associations that have been shown in more than one study have been CD13,3, 4, 5 CD14,3, 6, 7, 8 and CD155, 9. Many other markers for which claims of prognostic significance either alone or in combination have been made, have not been supported in other studies. The implication of co-expression of lymphoid antigens on myeloblasts has been of equally contentious prognostic significance.10, 11

In this review, we examine the evidence of the association of the immunophenotype of myeloblasts in adult AML with prognosis. We also include a series of 120 consecutive patients with de-novo AML from our institution examined in relation to the immunophenotype of myeloblasts seen at presentation and other recognized markers of prognosis.

Section snippets

Non-immunophenotypic prognostic markers in acute myeloid leukemia

Both clinical and biological features are used to predict the response to treatment in the heterogeneous group that is acute myeloid leukemia.¹² These can be used to predict response to induction chemotherapy and likelihood of subsequent relapse (Table 1).

Cytogenetic and molecular markers are particularly important in prognostic differentiation.2, 14 Using these, and other clinical and biologic markers, AML may be subdivided into three broad prognostic groups: favorable, standard (or

120 consecutive cases of AML

The Royal Melbourne Hospital (RMH) is a tertiary referral teaching hospital treating approximately 30-35 presentations of de-novo acute myeloid leukemia in adults each year. As part of the diagnostic evaluation for these patients, immunophenotyping of myeloid blast cells was performed. Bone marrow specimens from 120 consecutive patients presenting to Royal Melbourne Hospital between August 2000 and September 2003 with AML were analyzed. The diagnosis of AML was established according to the

Prognostic value of immunophenotyping in acute myeloid leukemia

The prognostic value of immunophenotyping in AML is controversial.10, 18, 19 Many of the studies that have found a positive association with expression of a single antibody and prognosis have been small, single institution studies, and few of these have been consistently reproduced in large, multi-institution trials.¹⁸ The comparability of the results is likely to be hampered by methodological differences in the detection of antigen expression as well as by the differences in patient

Conclusions

The prognostic implication of the immunophenotype of acute myeloid leukemia remains controversial. In part, the controversy has resulted from the fact that comparability of studies is hindered by methodological differences and advances in technology over the last 20 years. Earlier studies are also hampered by small numbers of patients. There has also been considerable difference in the number and specificity of antibodies examined in each study.

Of the more recent large studies of

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We observed that patients with AML with t(8;21) frequently expressed the surface antigens CD34, CD15, CD19, HLA-DR, and CD56; expression of CD11b was rare compared with other AML subtypes. As CD11b is known to be associated with poor prognosis in patients with AML [1], its rare appearance in AML with t(8;21) is in accordance with the good prognosis of patients with this subtype. It is also known that the expression of CD7 and CD34 is associated with poor clinical outcome in AML [1].
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Although MK has allowed for enhanced cytogenetic risk stratification in AML, the prognostic significance of immunophenotypes in the context of MK has not been addressed particularly in the cytogenetically high-risk population. In AML, flow cytometric immunophenotyping has been not only used for diagnosis but also to complement cytogenetic, morphologic and karyotypic findings for therapeutic management and prognostic prediction [12–15]. Expression of antigens such as CD7 [16,17], CD34 [18–21], CD11b [22–24] and CD56 [21,25] has been linked with inferior prognosis, while expression of CD15 [24,26,27] has been associated with a more favorable outcome.
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ReviewThe immunophenotype of acute myeloid leukemia: is there a relationship with prognosis?

Summary

Introduction

Section snippets

Non-immunophenotypic prognostic markers in acute myeloid leukemia

120 consecutive cases of AML

Prognostic value of immunophenotyping in acute myeloid leukemia

Conclusions

Blood

Blood

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Pathology

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Blood

Cancer Genet Cytogen

Leuk Res

Blood

Blood

Leuk Res

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Blood

Cancer Genet Cytogen

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Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome

Leukemia

Detection of minimal residual disease in acute leukemia by flow cytometry

Cytometry

Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia

J Clin Oncol

Prognostic value of immunological markers in acute myeloblastic leukemia. Leukemia

Immunophenotype of blast cells in acute myeloid leukemia may be a useful predictive factor for outcome

Hematol Oncol

Surface markers in adult acute myeloblastic leukemia:Correlation of CD19+, CD34+ and CD14+/DR– phenotypes with shorter survival. Groupe d’Etude Immunologique des Leucemies (GEIL)

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Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy

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Review
The immunophenotype of acute myeloid leukemia: is there a relationship with prognosis?