Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia.
We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable. In CMML survivin levels higher than in MDS and AML (P < 0.0001), but similar to those found in MPD were observed. In CMML and MDS apoptosis was significantly higher compared to normal controls and all other subtypes of leukemias (P < 0.0001). Proliferation did not differ significantly in normal controls, MDS and CMML; the lowest levels were observed in AML and MPD (P < 0.0001). In CMML there was no correlation between survivin expression and blast cell percentage, apoptosis or proliferation, FAB or WHO subgroup. Proliferation was higher in MDS-CMML and tended to correlate with overall survival. CMML-2 cases with higher survivin expression showed higher evolution rate and shorter survival. In conclusion, CMML is characterized by high proliferation and apoptosis. Survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may play an important role in its pathophysiology. The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments.
Invernizzi
Rosangela
R
Institute of Internal Medicine and Medical Oncology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy. r.invernizzi@smatteo.pv.it
Travaglino
Erica
E
Benatti
Chiara
C
Malcovati
Luca
L
Della Porta
Matteo
M
Cazzola
Mario
M
Ascari
Edoardo
E
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D002455:Cell Division; D018450:Disease Progression; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007951:Leukemia, Myeloid / Q000145:classification / Q000378:metabolism / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin