High expression levels of x-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia.
OBJECTIVE
Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare.


METHODS
Using flow cytometry and Western blot analysis, we, therefore, investigated 45 leukemic cell samples from children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins [CD95, Bcl-2, Bax, Bcl-xL, procaspase-3, X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein-1 (cIAP-1), survivin].


RESULTS
XIAP (P < 0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by French-American-British (FAB) morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (P < 0.01) and Bcl-xL (P < 0.01) expression was lower in patients with favorable rather than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP [30 (n = 10) versus 41 months (n = 34); P < 0.05] and survivin [27 (n = 10) versus 41 months (n = 34); P < 0.05].


CONCLUSIONS
We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups, and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics, and poor overall survival should be confirmed within prospective pediatric AML trials.
Tamm
Ingo
I
Department of Hematology, Oncology, and Tumor Immunology, Charité, Campus Berlin-Buch, Universitätsmedizin Berlin, Berlin, Germany. ingo.tamm@charite.de
Richter
Stephan
S
Oltersdorf
Doreen
D
Creutzig
Ursula
U
Harbott
Jochen
J
Scholz
Frank
F
Karawajew
Leonid
L
Ludwig
Wolf-Dieter
WD
Wuchter
Christian
C
D000293:Adolescent; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D051034:Inhibitor of Apoptosis Proteins; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012306:Risk; D000077022:Survivin; D013997:Time Factors; D016896:Treatment Outcome; D051636:X-Linked Inhibitor of Apoptosis Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis
C494826:BAX protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases