Biomedical Engineering Reference
In-Depth Information
ADHESION MOLECULES AS BIOMARKERS IN ACUTE
MYELOGENOUS LEUKEMIA
Many associations have been described between individual antigen expression
on myeloid blasts and prognosis; however, few are consistent. Some adhesion
molecules have been signii 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 signii 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 lympho-
hematopoietic 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, identii es a subgroup
of patients with a more unfavorable prognosis. On the basis of these i ndings,
Raspadori
et al
. (2001) evaluated CD56 surface expression in 152 newly diagnosed
acute myelogenous leukemia patients and demonstrated that it was signii cantly
associated with a reduced probability of achieving complete remission as well as
with a shorter survival. h ese results were coni 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. h 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
dif erentiation. h 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 specii c to CD44 (H90)
was able to eradicate acute myelogenous leukemia leukemic stem cells
in vivo
by
