Use of surface marker analysis to predict outcome of adult acute myeloblastic leukemia

Abstract

In order to investigate the clinical significance of surface antigen analysis in acute myeloblastic leukemia (AML), the blasts from 196 patients with AML were analyzed prospectively with a panel of 16 monoclonal antibodies. The antibodies were selected to identify differentiation-associated antigens of either the myeloid lineage (MY9, PM-81, AML-2–23, MY7, MCS-1, MY8, Mo1, MY1, MY4, Mo2), T cell lineage (T101, T11), B cell lineage (B1, B4) or multiple lineages [J5 (CALLA), HLA-DR]. Independent morphological review and classification by French- American-British (FAB) criteria was performed in 161 of the 196 cases. One or more myeloid surface antigens were detected on the blasts of 195 cases, while B and T cell markers were detected on 0% to 2% of cases. When both blood and marrow samples were studied on the same patient, very few differences were noted between the antigenic profiles of the paired specimens. The frequency of expression of individual myeloid antigens ranged from 91% (PM-81) to 29% (Mo2). Expression of individual antigens was found to correlate significantly with several clinical parameters including FAB classification, cytochemical staining for alpha naphthyl acetate esterase, leukocyte count, and the presence of extramedullary disease at presentation. Two myeloid antigens (MY4 and MY7) predicted for a low rate of complete remission (CR) to standard induction chemotherapy. MY4+ cases (37% of the total population) had a CR rate of 53%, while M4- cases had a CR rate of 69% (P = .03). MY7+ cases (57% of the total population) had a CR rate of 55% while MY7- cases had a CR rate of 73% (P = .01). Neither MY4 nor MY7 antigen expression was correlated with patient age. Paired combinations of antigens were also examined. The [MY4- MY7-] phenotype was exhibited by 32% of all cases and was associated with an 82% CR rate while the CR rate of all other cases was 54% (P = .001). The expression of three antigens (HLA-DR, MY8, Mo1) was associated with a decreased continuous complete remission (P less than .05, median follow-up time of 19 months). Expression of MY8 antigen was also associated with decreased survival (P = .03). These results confirm earlier reports of antigenic heterogeneity in AML, and indicate that immunologically defined subgroups of AML patients which are of potential clinical significance can be identified.

Relation of Blast Cell Survival and Proliferation to Chemotherapy Resistance in Aml

“…In conclusion, our present study indicates that two parameters are associated with high in vitro survival of AML blasts in vitro, namely, high CD13 expression and monocytic phenotype. This extends the findings of Griffin et al (1986) who demonstrated that the presence of CD13 or CD14 on AML blasts each were associated with inferior survival in patients treated with Dau Ara-C. In this context, it is also noteworthy that observed that FAB M4 and M5 were significantly associated to high autonomous proliferation in vitro, and that Campos et al (1993) noted that high Bcl-2 expression was associated with a monocytic phenotype.…”

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

“…Several studies have addressed the question of correlation between blast cell immunophenotype and FAB subtype in AML, and have arrived at conflicting conclusions (Drexler et al, 1986b; 0278-0232/90/0 10047-1 2 $06.00 0 1990 by John Wiley & Sons, Ltd. Kemnitz et al, 1987;Andreasen et al, 1986;Campos et al, 1987;San Miguel et al, 1986;Drexler and Minowada, 1986;Pessanon et al, 1984;Linch et al, 1984;Griffin et al, 1986;Van Rhenen et al, 1983). Studies relating blast cell phenotype to prognosis have been fewer, and again have yielded different results Holowiecki et al, 1986) which may be due in part to their multicentric nature.…”

“…The ideal panmyeloid marker for use in diagnostic immunophenotyping in leukemia has yet to be found and analysis still relies upon the use of multiple combinations of antibodies. This single centre study has demonstrated that blast cell immunophenotype in AML is usually CD13 and CD33 positive confirming previous studies (Messner and Griffin, 1986;Griffin et al, 1986), but more commonly is SC9 positive. This latter antigen is at present poorly defined (Hogg and Horton, 1987); our findings suggest that it merits further investigation.…”

“…In the CALGB study (Griffin et af., 1986) there was a shorter first CR in patients who were HLA-DR and CD11 b-positive, but, again, we could not confirm this. Griffin et al (1986) reported an association between expression of CD14 and CD15 with patient survival. However, although we did not see such a relationship, a correlation was observed with CD14 if a threshold for 'positivity' of 50 percent was used, as opposed to a convential 20 per cent cutoff.…”

The presence of leukaemia‐associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia

“…Hence, LAP may have an association with prognosis and response to treatment. There are many studies looking at the prevalence of LAP in AML and their clinical usefulness (Bahia et al, 2001;Griffin et al, 1986;Macedo et al, 1995b). Most focus on aberrant expression of individual antigens like CD7, CD14 and CD56 (Del Poeta et al, 1995;Norgaard et al, 2001;Raspadori et al, 2001;Tiftik et al, 2004).…”