ABSTRACT
Many associations have been described between individual antigen expression on myeloid blasts and prognosis; however, few are consistent. Some adhesion molecules have been signifi cantly related with a prognostic association such as CD15, CD11b, CD34 and CD56. CD15 is cell surface glycoprotein that is the ligand of E and P selectins, expressed on maturing cells of monocyte lineage and more weakly on maturing cells of granulocyte lineage. Tien et al. (1995) found that CD15 and CD11b were of prognostic value: CD15 with a higher complete remission rate and CD11b with a shorter complete remission duration. CD34 is a monomeric cell adhesion molecule of the syalomucin family that is expressed on leukemic blasts and hematopoietic stem cells. CD34 positivity has been correlated with a poor response to induction chemotherapy in acute myelogenous leukemia patients. Raspadori et al. (1997) investigated the expression of CD34 antigen on leukemic cells in 141 adult patients with diagnosis of acute myeloid leukemia. In patients whose blasts expressed CD34 antigen, a signifi cantly lower rate of complete remission was observed than in CD34-negative cases (61% vs 88%), suggesting that a high CD34 intensity of expression should be considered as a reliable poor prognostic factor. CD56 antigen has been found frequently expressed in several lymphohematopoietic neoplasms. In fact, it has been reported that the presence of CD56 antigen on the blasts of acute myelogenous leukemia patients with t(8;21) (q22;q22), and in those with acute promyelocytic leukemia, identifi es a subgroup of patients with a more unfavorable prognosis. On the basis of these fi ndings, Raspadori et al. (2001) evaluated CD56 surface expression in 152 newly diagnosed acute myelogenous leukemia patients and demonstrated that it was signifi cantly associated with a reduced probability of achieving complete remission as well as with a shorter survival. Th ese results were confi rmed by other authors, showing that in general the expression of CD56 in acute myelogenous leukemia is a ‘negative prognostic marker’. CD56 expression also has been correlated with extramedullary disease. Th is could be explained by the hypothesis that CD56-expressing blasts can bind to β3 integrins on endothelial cells and are thus responsible for the higher incidence of extramedullary manifestations in CD56+ leukemias. Another molecule associated with prognosis is the CD44 antigen, which on leukemic blasts from most acute myelogenous leukemia patients is involved in myeloid diff erentiation. Th e expression of variant forms of CD44 has been associated with poor prognosis in acute myelogenous leukemia. CD44 displays many variant isoforms (CD44v) generated by alternative splicing of exons 2v to 10v. Legras et al. (1998), demonstrated that the expression of CD44-6v correlates with a shorter survival of patients treated with conventional chemotherapy. CD44 is a potential therapeutic target, and treatment with an activating mAb specifi c to CD44 (H90) was able to eradicate acute myelogenous leukemia leukemic stem cells in vivo by
blocking leukemic stem cells traffi cking to supportive microenvironments and by altering their stem cell fate in a NOD/SCID xenotransplant model (Jin et al. 2006). Taken together, the experimental and clinical data discussed above demonstrate that signaling through adhesion molecules is essential for the regulation of hematopoieses, and their aberrant expression and function provide a survival advantage to leukemic cells. Th erefore, an ever-increasing number of studies corroborate the idea that adhesion molecules are important biomarkers and targets for the development of new therapeutic strategies.
