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

Abstract

The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.

Immunological classification of acute myeloblastic leukemias: relevance to patient outcome

“…This report highlights specifically the fact that the prognostic value of an individual antigen's expression depends on the immunological differentiation stage of the leukemic cells. The present study demonstrated that antigens whose expression had already been shown as a potential prognostic factor (CD34,-CD7,-CD14) (19)(20)(21)(22)(23)(24)(25)(26)(27)(28) were indeed related to outcome in the overall population. More interestingly, their prognostic value, which could be marginal in the overall population, became strongly significant in specific immunological AML subsets while it retained no significance in other subsets.…”

“…The frequency of CD34 expression was similar in these two subsets as compared to other immunological AML subsets, and was not related to specific FAB subgroups, which indicates that MA and MD indeed define specific entities. Conversely, CD14, more frequently expressed in AML with a monocytic component, (21)(22)(23)30) appeared related to a poor outcome only in MD and ME subsets. The prognostic value of CD14 expression was independent of the FAB classification in the MD subset and had already been reported in such FAB subsets as M3 (22) or M0.…”

MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia

“…Higher age, high white blood cell count at diagnosis, and M 0 morphology have been recognized as clinically adverse prognostic factors in AML. Additional biological or disease-related prognostic variables which are associated with a poor survival include higher age, hyperleucocytosis, autonomous leukaemia growth in vitro, expression of the immature stem cell antigen CD34 and karyotypic abnormalities such as monosomy 7, 5q¹, 7q¹, the Philadelphia chromosome (t(9;22) and a complex karyotype (Campos et al, 1989;Löwenberg et al, 1993;Machnicki & Bloomfield, 1990). On the other hand, cytogenetic abnormalities such as inv(16), t(8;21) and t(15;17) are associated with a good response to chemotherapy.…”

Acute myeloid leukemia cells with low P-glycoprotein expression and high Rhodamine 123 efflux capacity display high clonogenicity

“…In fact, the CD34 glycoprotein, which is expressed on immature myeloid cells, has been generally correlated with lower remission induction rate and shorter overall survival. [3][4][5][6][7][8][9][10] Among different mechanisms considered responsible for the chemoresistance of immature myeloid leukemic cells to DNR, the multidrug resistance phenotype (MDR) appears to play an important role. Indeed, in bulk leukemic cells taken from the blood or the marrow of patients with de novo or secondary AML, as well as in AML cell lines, CD34 expression has been correlated with both the mdr1 gene and P-glycoprotein (Pgp) overexpression.…”