Immunological detection of blast cell subpopulations in acute myeloblastic leukemia at diagnosis: implications for
A Macedo1, A Orfão, M Gonzalez
1Servicio de Hematología, Hospital Clínico Universitario, Salamanca, Spain.
Insights
Most acute myeloid leukemia (AML) patients have multiple blast cell subpopulations at diagnosis, identified by immunophenotype. These minimal subpopulations can drive relapse, highlighting the need for precise minimal residual disease (MRD) monitoring.
Area of Science:
- Hematology
- Immunology
- Flow Cytometry
Background:
- Acute myeloid leukemia (AML) is characterized by the proliferation of immature myeloid cells.
- Minimal residual disease (MRD) detection is crucial for predicting relapse in AML patients.
- Blast cell heterogeneity at diagnosis may influence treatment response and relapse risk.
Purpose of the Study:
- To determine the incidence of multiple blast cell subpopulations in de novo AML using immunophenotyping.
- To analyze the phenotypic characteristics and aberrations of these subpopulations.
- To assess the implications for minimal residual disease (MRD) monitoring.
Main Methods:
- Prospective immunophenotypic analysis of blast cells from 40 de novo AML patients at diagnosis.
- Utilized a comprehensive panel of monoclonal antibodies with double and triple staining.
- Flow cytometry was employed to analyze cell populations based on aberrant phenotypes, light scatter, and differentiation antigens.
Main Results:
- Multiple blast cell subpopulations were identified in 85% of patients.
- Minimal subpopulations (<10% of leukemic cells) were present in 53% of cases.
- Aberrant phenotypes were observed in various combinations, with common aberrant criteria found in 74% of patients with multiple aberrant subpopulations.
Conclusions:
- The presence of multiple blast cell subpopulations is common in de novo AML.
- Minimal blast subpopulations can be phenotypically distinct and may contribute to relapse.
- Identifying common aberrant phenotypes is crucial for effective MRD monitoring strategies in AML.
Abstract:
The aim of the present study was to analyze the incidence of AML cases displaying more than one blast cell subpopulation by immunophenotype at diagnosis, since, any of them, although minimal, can be responsible for the relapse. For this purpose we have prospectively investigated the immunophenotype of blast cells from 40 de novo AML patients at diagnosis with a large panel of monoclonal antibodies in double and triple staining combinations analyzed at flow cytometry. The discrimination between the different cell populations was based on: (1) the existence of aberrant phenotypes; (2) differences in light-scatter characteristics; and (3) the expression of differentiation-associated antigens (CD34, CD117, HLADR, CD33, CD15, CD14, CD11b and CD4). More than one blast cell subpopulation was identified in 34 patients (85%), two subpopulations in 12 patients (30%), three in three cases (7.7%), four in 13 patients (32.5%) and five populations in six cases (15%). The most common criteria for discrimination of blast cell subpopulations was based on the expression of maturation-associated antigens and, interestingly, the blast subpopulations defined by higher reactivity for myeloid differentiation-associated markers had a more mature FSC/SSC pattern. In 53% of the patients at least one of the subpopulations identified was minimal (< 10% of the total leukemic cells). Regarding the existence of aberrant phenotypes three situations were observed: (1) none of the subpopulations had antigenic aberrations (10 cases); (2) coexistence of normal and aberrant subpopulations (five cases); and (3) all the subpopulations displayed aberrant phenotypes (19 cases). In 17 of the 23 patients (74%) who had two or more blast cell subpopulations with phenotypic aberrations, at least one aberrant criteria was common to all the subpopulations; this criteria by itself would permit the simultaneous identification of all subpopulations in minimal residual disease (MRD) studies. In the remaining cases the investigation of MRD should be based on the phenotypic characteristics of each subpopulation.
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