Antigens As Predictors Of Prognosis

Reports on the prognostic significance of single antigens have to be viewed with caution if they are based on small numbers of patients, if they are unconfirmed, if data are not reported on gated blast cells, or if arbitrary cutoff points of antigen expression were used to determine positivity. To date, few antigens are unequivocally associated with clinical response.

CD56, the neural cell adhesion molecule, is an indicator of poor treatment outcome, particularly short remission duration, both in APL22,23 and in AML with t(8;21).24 Acute myeloid leukemia expressing the immature monocytic antigen and inte-grin CD11b was postulated to represent a new leukemic syndrome based on a large database analysis of the Eastern Cooperative Oncology Group (ECOG).25 The result of this prognosis-driven retrospective analysis supported previous suggestions of CD11b as a marker for shortened survival in AML.26-29 Whether this negative effect on outcome seen with CD56 as well as CD11b is related to their function as adhesion molecules is currently unclear. Obviously, it is of great interest when the clinical significance of an antigen finds an explanation in its biologic properties. This may be the case with CD10 and its favorable prognostic implications when expressed in both pediatric and adult T-lineage ALL.30,31 In normal lymphopoiesis, CD10 marks T cells induced to undergo apoptosis.32,33

Two examples of antigens whose prognostic significance had to be reconsidered based on larger data files or methodology of analysis are the stem cell growth factor receptor, c-kit or CD117, and the T cell-associated antigen, CD7. Both were initially reported to confer poor prognosis in AML. For CD117, increasing the number of patients analyzed demonstrated its broad spectrum of expression in AML subtypes irrespective of the level of myeloid differentiation, its characteristic occurrence in APL, its absence in acute monocytic leukemia, its exceedingly rare incidence in ALL, and its value for monitoring minimal residual disease; however, this did not confirm any prognostic impact.2,34-39

In the case of CD7, several reports have suggested the unfavorable outcome of patients with CD7+ AML when compared with CD7- AML patients, although other studies have argued against this. All of these studies arbitrarily used 20 percent pos itive blast cells as the definition of CD7+ AML. In a retrospective analysis, Kornblau et al.40 found more than 10.5 percent of CD7+ myeloblasts to produce the largest survival difference between CD7+ and CD7- AML according to this criterion. However, there was no statistically significant survival difference between the two groups. That antigens may have a pivotal role in predicting certain clinical behavior, thereby indirectly affecting prognosis, is only starting to be appreciated. Expression of CD13, an aminopeptidase, has been linked to the development of the retinoic acid syndrome (RAS) in APL patients treated with ATRA.41 Another postulated culprit in the development of RAS in response to ATRA or arsenic trioxide is CD38, an ectoenzyme involved in the metabolism of NAD+.42 Both agents are potent inducers of CD38, which, through interplay with its ligand CD31 expressed by endothelial cells, may alter the propensity of the leukemic promyelocytes to adhere to the vessel walls as well as to initiate cytokine release. The increased incidence of granulocytic sarcomas in AML with the 8;21 translocation43 may be related to the expression of the neural cell-adhesion molecule CD56.44

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