Immunological classification of acute myeloblastic leukemias: relevance to patient outcome

Abstract

Immunophenotyping is a major tool to assign acute leukemia blast cells to the myeloid lineage. However, because of the large heterogeneity of myeloid-related lineages, no clinically relevant immunological classification of acute myeloblastic leukemia (AML) has been devised so far. To attempt at formulating such a classification, we analyzed the pattern of expression of selected antigens, on blast cells collected at AML diagnosis. Patients were eligible if they had a first diagnosis of de novo AML and a sufficient number of blast cells for proper immunophenotyping. The relative expression of CD7, CD13, CD14, CD15, CD33, CD34, CD35, CD36, CD65, CD117, and HLA-DR were analyzed by cytometry in a test series of 176 consecutive AML cases. Statistical tools of clusterization allowed to remove antigens with overlapping distribution, leading us to propose an AML classification that was validated in a second AML cohort of 733 patients. We identified five AML subsets (MA to ME) based on the expression of seven antigens within four groups (CD13/CD33/CD117, CD7, CD35/CD36, CD15).-MA and MB-AML have exclusively myeloid features with seldom extramedullary disease and rare expression of lymphoid antigens. No cases of acute promyelocytic leukemia (APL) were observed within MB AML. MC AML have either myeloid or erythroblastic features. MD AML have more frequently high WBC counts than other subsets, which were related to the expression of CD35/CD36 and CD14 and to monoblastic differentiation. ME AML lack CD13, CD33, and CD117 but display signs of terminal myeloid differentiation. Specific independent prognostic factors were related to poor overall survival in each immunological subset: CD34+ (Po3 Â 10 À4 ) in MA AML, CD7+ in MB AML, non-APL cases (Po0.03) in MC AML, CD34+ (Po0.002) and CD14+ (Po0.03) in MD AML, CD14+ in ME AML (Po0.01). The inclusion of seven key markers in the immunophenotyping of AML allows a stratification into clinically relevant subsets with individual prognostic factors, which should be considered to define highrisk AML populations.

Flowcytometric Immunophenotypic Profile of Acute Leukemia: Mansoura Experience

“…Expression of CD117 was seen in 72.4% of non-APL AML cases and in 80.8% of APL cases. Similar findings were reported by previous studies [18][19][20]. So, MPO and CD117 are not reliable markers for differentiation between APL and non-APL AML.…”

Immunophenotyping of acute leukemias and myelodysplastic syndromes

“…In other subtypes of AML, it is frequently claimed that immunophenotyping just stands for confirmation of morphological, cytochem- ical, and genetic diagnoses (69). In line with this and in contrast to what was described above for ALL, there is still no accepted immunological classification for AML (70). In summary, these results point out the relatively limited utility of individual markers in AML as well as the need for more powerful multiparameter immunophenotypic analytical approaches as also discussed below for MDS.…”

Profiling CD antigens on leukaemias with an antibody microarray

“…Cell surface profiling of CD antigens is especially important in the diagnosis of acute lymphoblastic leukaemia (ALL), helping to indicate the subtype of cell using lineage-specific antigens and to distinguish undifferentiated acute myeloid leukaemia (AML) from ALL [1]. Several groups have investigated the possibility of diagnosing leukaemias based solely upon immunophenotype [4,5] Abbreviations: ALL, acute lymphocytic leukaemia; AML, acute myeloid leukaemia; APL, acute promyelocytic leukaemia; ATRA, all-trans retinoic acid; BMA, bone marrow aspirate; CD antigen, cluster of differentiation antigen; CEA, chorioembryonic antigen; CLL, chronic lymphocytic leukaemia; 1,25D 3 , 1-a,25-dihydroxyvitamin D 3 ; CRC, colorectal cancer; EpCAM, epithelial cell adhesion molecule; HLDA, human leukocyte differentiation antigens; TILs, tumour-infiltrating lymphocytes; PB, peripheral blood; TPA, 12-O-tetradecanoyl phorbol-13-acetateidentify a limited profile of CD antigens for each clinical condition. Flow cytometry is labour-intensive, expensive and enables parallel measurement of only a small number of antigens.…”

“…A number of analogues of 1,25D 3 : EB1089, MC903, RO24-5531, 1-a-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , 19-nor-1-a,25-dihydroxyvitamin D 2 and 1-a-hydroxyvitamin D 5 , induce differentiation without hypercalcaemia. These analogues have passed stringent pre-clinical toxicity trials in animals [43].…”