XIAP expression correlates with monocytic differentiation in adult de novo AML: impact on prognosis.
Antiapoptotic proteins like the inhibitor of apoptosis proteins (IAPs) are molecular markers potentially useful for the characterization of acute myeloid leukemia (AML). We screened 92 adults with de novo AML for the protein expression of various IAPs, Bcl-2 family members and the proform of Caspase-3 using quantitative immunoblot and flow cytometry. XIAP expression correlated with myelomonocytic French-American-British (FAB) subtypes M4/M5 (P < 0.05) and expression of monocytic markers (CD 14, CD 36; P < 0.05; CD 4, HLA-DR; P < 0.01) in AML blasts. In addition, XIAP was overexpressed in normal monocytes but undetectable in granulocytes. In AML, XIAP expression was significantly lower in patients with favorable than intermediate or poor cytogenetics (n = 74; P < 0.05). In total, 62 of the examined patients were treated according to the German AML Cooperative Group (AMLCG) 92 protocol. These patients were analyzed for prognostic significance of apoptosis-related proteins. Patients expressing low levels of XIAP enjoyed better overall survival than patients expressing high amounts of XIAP (mean, 9 (n = 41) versus 19 months (n = 21); P < 0.05). Other IAPs, most importantly Survivin, were of no prognostic value. We conclude that XIAP but not other IAP family members is associated with monocytic differentiation in normal and malignant myelopoiesis, and may be of prognostic significance for overall survival in adult de novo AML.
Tamm
Ingo
I
Department of Hematology and Oncology, Universitätsmedizin Berlin, Charité, Berlin, Germany. ingo.tamm@charite.de
Richter
Stephan
S
Scholz
Frank
F
Schmelz
Karin
K
Oltersdorf
Doreen
D
Karawajew
Leonid
L
Schoch
Claudia
C
Haferlach
Torsten
T
Ludwig
Wolf-Dieter
WD
Wuchter
Christian
C
D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019044:Image Cytometry; D016130:Immunophenotyping; D051034:Inhibitor of Apoptosis Proteins; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012307:Risk Factors; D016019:Survival Analysis; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein
D000943:Antigens, Differentiation; 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; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases