Inhibitor Of Apoptosis Protein Survivin Expression In Myeloproliferative Disorders And Their Significance

Objective To investigate the expression of Survivin and its clinical implication in CMPD.Methods The expression of Survivin protein in bone marrow mononuclear cells was measured by western blot in 21 ET,12 PV and 12 chronic myelogenous leukemia(CML) patients as well as five healthy donors.K562 cells were tested as a positive control.β-actin was used as an internal control.The relative levels of Survivin expression in each sample were calculated by normalizing to the levels ofβ-actin.The correlation between Survivin expression levels and blood cell counts was determined by drawing the best-fit linear curve with Regression Analysis.Results Survivin expression was observed in 23.3%(5 of 21) cases in ET, 66.8%(8 of 12) in PV and 83.3%(10 of 12) in CML,but undetected in the five healthy donors.The positive rate of Survivin expression in PV and CML was markedly higher than that in ET(P=0.02 and P=0.001) and healthy group. Survivin expression levels in all patients correlated with WBC count of peripheral blood and with megakaryocyte count of bone marrow.When analyzing 3 groups of CML,ET and PV separatively,we found that Survivin expression levels correlated with peripheral blood WBC count and with the percentage of peripheral blood blast cell in CML group,but not in ET and PV groups. However,Survivin expression levels in PV group was associated with the amount of Hb.In contrast,the levels of Survivinwere reverse to the amount of Hb in CML group.Moreover,the levels of Survivin in ET group has no significant relationship with WBC count,Hb,PLT count,JAK2V617F or the percentage of blast cell in bone marrow.Conclusions The different profile of Survivin expression in CML,PV and ET might reflects its different roles in these diseases.In CML,the aberrant expression of Survivin might happen earlier in blast cell and correlated with the percentage of blast cells.The correlation of Survivin and Hb in PV suggests a role of Survivin in Excessive and abnormal erythropoiesis. To summarize the clinical feature and natural course of essential thrombocy-themia (ET) in China,A retrospective analysis was conducted in ET patients treated in our hospital during May 1980 and December 2006.In this period,438 patients(201 males and 237 females with a median age 48 years) were diagnosed in our hospital, hemorrhage occurred in 101 cases(23.1%),thrombosis occurred in 86 cases(19.6%), and 13 cases(3.0%) had both hemorrhage and thrombosis.Splenomegaly occurred in 150 cases and hepatomegaly occurred in 60 cases.One hundred and forty-nine cases (34%) had no symptoms at diagnosis and 145 cases(33.1%) confirmed by routine blood tests due to other diseases.The median platelet count at diagnosis was 1,000×10~9 /L(533～3,740×10~9/L).Bone marrow biopsy was performed in 255 cases showing mainly increase of enlarged mature megakaryocytes with hyperlobulated nuclei and local proliferation of reticular fiber were revealed in 51 cases.JAK2V617F mutation was detected in 90(78.9%) of the 114 patients.Karyotype analysis was performed in 180 cases and 6 cases(3.3%) had clonal chromosomal aberrations.Two hundred and sixty-one patients were followed-up over 12 months with a median follow-up period of 60 months(range from 12 to 300 months).Seventeen cases(6.5%) evolved into marrow fibrosis(MF) and one case evolved into polycythemia vera(PV).One case evolved into PV after 6 years and MF after 20 years.Three cases developed acute monocyte leukemia(MS),myelodysplastic syndrome(MDS) and multiple myeloma (MM),respectively.ET is a chronic myeloproliferative disorder characterized predominately by thrombocytosis and hemorrhage.The percentage of asymptomatic cases is high.The main sequelae of ET is MF and most cases have good prognosis. Objective To summarize the cytogenetic characteristics and their clinical significances of the patients with essential thrombocythemia(ET) in China.Methods Cytogenetic findings of 180 patients with ET were retrospectively analysed and the clinical implications of specific chromosomal abnormalities(CA) were investigated.Result1.Cytogenetic findings:clonal CAs were detected in 6 of 180 patients(3.3%) by conventional cytogenetics(CC);In the numerical aberrations,the most common trisomies were 6,1 and the most common monosomies were 21,followed by 8, 13,14,18 and Y.In the structural aberrations,the most frequently involved arms were 9q,11q and 20q,and the most frequently involved breakpoints were 9q12～31,11q14,20q11～12 and 5q13～31.2.Clinical implications:there was no significant difference between the clinical characteristics of chromosomal abnormalities group and normal control,however the latter have a higher efficiency in therapy.ConclusionsThe occurency of CA in patients with ET from China is mildly lower than those from western country.The chromosomes numerical aberrations and deletant or addend of chromosomes arms are main abnormal in CA,but translocation occur seldom.Clonal CAs often display single clonal CA or company with other subclonal CAs.All chromosomes can be involved in CAs.The occurancy of +8 in patients of ET from China is obviously lower than those from western country,but chromosome 9 and 21 can be involved more frequency.