Survivin expression in "low-risk" and "high-risk" myelodysplastic syndromes.
Apoptosis has a crucial role in myelodysplastic syndromes (MDS), being responsible of the ineffective hematopoiesis characteristic of the disease. Apoptosis rate is elevated in "early phase" MDS, whereas it diminishes during disease progression to acute leukemia, consensually to the acquisition of independent growth features. Survivin is a member of the inhibitor of the apoptosis (IAP) family, with the bifunctional role of suppressing apoptosis while facilitating cell cycle progression. We investigated Survivin mRNA levels by real-time quantitative reverse transcriptase PCR analysis and Survivin protein expression by immunohistochemistry in 49 bone marrow (BM) aspirates and in 17 BM biopsies (BMB) from MDS patients. Survivin mRNA levels were higher in MDS than in control group (1.68 +/- 1.46 vs 0.25 +/- 0.22; p < 0.0001). MDS patients with low or INT1 International Scoring System for Evaluating Prognosis (IPSS) displayed higher levels of Survivin mRNA in comparison to INT2 or high IPSS (1.91 +/- 1.51 vs 0.88 +/- 0.95; p = 0.0058). Survivin protein immunoreactivity was evaluated as Survivin index S ((i)) and calculated according to the formula: S ((i)) = % of Survivin positive cells x BMB cellularity / 100. Survivin index was higher in the MDS group than in normal BM (p = 0.05). Moreover, in eight cases in which BM aspirates and trephine biopsy were available, we found a significant association between the level of Survivin mRNA and protein expression (p = 0.011). In conclusion, this study demonstrates increased levels of Survivin in MDS compared to normal controls. Moreover, higher levels of transcripts are related to "low-risk" MDS. Our results suggest an active role of Survivin in normal and in myelodysplastic hematopoiesis.
Gianelli
Umberto
U
II Cattedra di Anatomia Patologica, Dipartimento di Medicina, Chirurgia e Odontoiatria, Università degli Studi di Milano, A. O. S. Paolo e Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano, Italy. umberto.gianelli@alice.it
Fracchiolla
Nicola Stefano
NS
Cortelezzi
Agostino
A
Pellegrini
Caterina
C
Savi
Federica
F
Moro
Alessia
A
Grimoldi
Maria Grazia
MG
Deliliers
Giorgio Lambertenghi
GL
Coggi
Guido
G
Bosari
Silvano
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin