Correlation between High Expression of Natural Killer Related-Genes (NCAM/CD94) and Early Death during Induction in Children with Acute Myeloid Leukemia.

Death early (DE) during the induction phase of therapy is a rare but dramatic event in children with acute myeloid leukemia (AML). Recent reports emphasize that DE in patients with leukemia is related to aggressive disease, signaled by hyperleukocytosis, and to the early administration of intensive chemotherapy. Many efforts have been made to better characterize subgroups of patients with AML by defining biologic markers associated with aggressive disease. Even if little is known about the molecular mechanisms that regulate blast migration into tissues, adhesion receptors are likely to play an important role in this process. We have attempted to identify the molecular characteristics of an aggressive subset of pediatric patients with AML through a prospective evaluation of the CD56 + neural cell adhesion molecule (NCAM) and CD94 expression. For this purpose we developed an RT-PCR semi-quantitative methodology, using specific primers from NCAM, CD94 and β-actin as an internal quality and quantity control. We analyzed a total population of 44 children with AML, distributed as follow: 5 with M3v (group A), 9 with APL (group B) and 30 with non-APL AML (group C). We found a dramatic correlation in group A between high expression of NK-related genes and occurrence of early death. In groups B and C, primarily used as controls, we found a strong correlations between a high level of NCAM-CD94 expression and two cases with APL, three with FAB M5, two with FAB M2 AML, one case with FAB M4 and a child with dendritic cell leukemia (DCL). We primarily found that 9 out of 13 cases presenting with a high level of NCAM-CD94 expression died of disease-related events during the early days of induction. Our data strongly suggest that doses and timing of chemotherapy induction in children with AML need to be modulated because of the high risk of hemorrhagic events. These appear to be related to the presence of high concentration of adhesion molecules secondary to acute blast lysis and to the associated severe coagulopathy. We know of no pharmacological correctives for this phenomenon. It would be important to develop specifically designed molecules in order to disrupt the interactions with adhesion molecules, and thus to improve the clinical course of both children and adults with AML during the early days of induction.