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

Abstract

The immunophenotype of peripheral blood blast cells was tested in 92 patients with acute myeloid leukemia (AML), who were diagnosed and treated at single centre, St Bartholomew's Hospital, from 1978-1987 with a standard adriamycin, cytosine arabinoside and 6-thioguanine regimen. Immunological analysis involved standard fluorescence flow cytometry and utilized 31 monoclonal antibodies to known myeloid antigens (of CD groups 11b, 11c, 13, 14, 15, 16, w17, 31, w32, 33, 34, 35 and 36), a number of relatively less well studied antibodies with potential specificity for AML, and a series of control antibodies to T and B lymphocytes, platelets, erythrocytes and of widespread distribution (CD45, leucocyte common; HLA-DR). The results highlighted a number of antibodies with wide myeloid reactivity, in addition to CD13 and 33 (present in 66 per cent and 76 per cent of cases, respectively), which may be of immunodiagnostic use. A number of correlations between AML cell immunophenotype and FAB morphology subtype were found; in particular five antibodies (CD11c, 10.1, Tu3, CD15 and CD16), of both predominant granulocytic and monocytic reactivity, reacted with cells of AML-M5 subtype (p less than 0.05). There was no significant correlation between immunophenotype and clinical and pathological features at presentation. Correlation with clinical outcome was not a prominent feature, in contrast to some reports based on multicentre data. However, of particular note was the strong association between early death (at less than 2 months) and the coexpression of Leucocyte Function Associated (LFA) antigens, CD11b and 11c, on patient's blast cells (p = 0.003). The relationship was independent of clinical features and persisted even if AML-M5 cases were excluded. The significance of this latter finding is unclear, but may be related to the known role of CD11b and 11c LFA antigens in the cellular response to infection.

HLA-DR antigen-negative acute myeloid leukemia

“…51 CD34 is expressed in approximately two-thirds of non-APL AML cases. 18,[52][53][54] We asked whether a unique immunophenotype could serve to distinguish between APL and HLA-DR-negative cases with other AML subtypes. We found that these two groups could not be separated based on the panels of antigens analyzed in this study.…”

Acute myelogenous leukemia blasts as accessory cells during T lymphocyte activation: possible implications for future therapeutic strategies

“…Clinical studies in allogeneic bone marrow transplant recipients Increased risk of leukemia relapse, decreased risk of GVHD and transplant-related mortality in identical twin transplants 10 Complete remission has been observed after treatment of post-transplant AML relapse with donor leukocyte transfusions [12][13][14][15][16][17] The frequencies of host reactive helper and cytotoxic T lymphocytes in stem cell donors correlate with the risk of GVHD 23,24 Cytotoxic T cells recognizing minor histocompatibility antigens can inhibit AML blast proliferation 27 AML blasts expression of membrane molecules necessary for antigen-specific T cell activation AML blasts express HLA class I and class II molecules which are capable of presenting processed antigenic peptides [29][30][31][32][33][34][35][36][37][38][39][40] AML blasts express molecules mediating costimulatory signals (LFA-3, ICAM-1, B7.1, B7.2) effects during antigen-specific T cell activation 29,71,[99][100][101][102][103][104] Normal T cell recognition of leukemia-specific antigenic peptides…”

“…Hirano et al 29 investigated AML blasts derived from 92 patients, and all cases were positive for HLA class I and with a strong expression on Ͼ90% of the blasts for 89 out of the 92 patients. For most patients the AML blasts express HLA-DR molecules also, [29][30][31][32][33][34][35][36][37][38][39][40] but the expression of other class II molecules is less well characterized. HLA class II expression is independent of FAB classification, the only exception being the AML-M3 subtype where significantly lower levels of class II expression are detected.…”

“…HLA class II expression is independent of FAB classification, the only exception being the AML-M3 subtype where significantly lower levels of class II expression are detected. [30][31][32] Thus, for the large majority of patients AML blasts express the self-HLA molecules needed for presentation of antigenic peptides to T lymphocytes. However, several studies have demonstrated that this HLA class II expression can vary between different AML blast subsets even within the same patient.…”

“…35 Although two studies have addressed the question whether this intra-and interpatient variation in HLA class II expression is important for the outcome after chemotherapy, it is still too early to make an answer to this question. 30,39 Leukemia-specific antigenic peptides and their binding to HLA molecules The chromosomal translocations often involve components of the transcription machinery, and the expressed fusion proteins may then result in fundamental alterations in the regulation of cell proliferation or apoptosis. [42][43][44][45][46] At the same time expression of fused or mutated proteins forms a molecular basis for the expression of leukemia-specific peptide sequences.…”