Abstract 4717

Background

Several anti apoptotic signals have been recently identified. Aven and Survivin are broadly expressed and are conserved in mammalian species.

Patients and Methods

Sixty-four patients with acute leukemia [39 with acute myeloblastic leukemia (AML) and 25 with acute lymphoblastic leukemia (ALL)] were used as the study group. Reverse transcriptase (RT –PCR) was used, Aven and Survivin expression were detected at the messenger (mRNA) level .DNA fragmentation was carried out on daily basis before &24 hours after the therapeutic dose every day for 4 times during the initial induction of chemotherapy (everyday for ALL& every otherday for AML).

Results

Survivin expression was found in (66%) of acute leukemia, near significantly (p=0.06) more in AML (74%) than in ALL (52%). While, Aven expression was (40.6%) in acute leukemia equally expressed in AML (41%) and ALL (40%).Patients were categorized into 3 groups based on DNA fragmentation, whereby group I: DNA fragmentation found on day 1 or day 1+day 2, group II: DNA fragmentation found on days 1, 2 and 3, group III where fragmentation was found on days 1+2+3+4 or/and day5. Absence of Aven expression significantly (p<0.001) contributed to DNA fragmentation as 24 /35 (68.6%) of acute leukemia with Aven negative were in group III (the best group). Absence of Survivin did not contribute as much, Where 18 out of 31 (58%) of group III were Survivin positive (P= 0.1).None of the concordant both positive Survivin and Aven were in group III (the good 5 day fragmentation), this was statistically highly significant (P< 0.001) relation. Survivin was statistically related to CD7 expression (P<0.001) in AML only, while Aven was statistically related to CD34 expression (P<0.014) in the whole acute leukemia cases. Aven was statistically correlated to alkaline phosphatase (P< 0.036).There was a significant dissociation between Aven and Survivin in AML (p=0.03) and near significant dissociation in ALL (p=0.07).

Conclusion

Aven seems to be more important as an inhibitor of apoptosis than survivin in acute leukemia. The presence of both Aven & survivin confers a survival disadvantage & a significantly worse DNA fragmentation pattern, thus suggesting a synergistic inhibition of apoptosis when present together, although, they tend not to be expressed together. The highly significant relation between CD7 & surviving expression, might suggest their involvement in a common signal transduction pathway.

Key words: Survivin, Aven, AML, ALL and DNA fragmentation.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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