BAP1 And TET2 Protein Predict The Prognosis Of Chronic Myelomonocytic Leukemia

Purpose1. To investigate the expression of BAP1 and TET2 protein in patients with chronic myelomonocytic leukemia (CMML) and the impact on the prognosis of CMML.2. To determine the clinical characteristics and prognostic factors of CMML.3. To investigate whether there is correlation between expression of BAP1 and TET2 protein in CMML cases.4. To study BAP1 protein and TET2 protein expression differences among CMML、 acute myelomonocytic leukemia (AMML) and iron deficiency anemia (IDA).MethodsA retrospective cohort study was used in the research. We investigated clinical and laboratory characteristics of CMML patients and survival status. Patients were followed up regularly through out the course of the research. We detected BAP1 and TET2 protein expression in paraffinsection of cases by immunohistochemistry, which included 41 newly diagnosed CMML patients,40 cases of newly diagnosed AMML and 20 newly diagnosed IDA as the control.Kaplan-merier curve method was used to calculate the median survival time. Pearson correlation analysis was used to analyse the correlation between the expression of BAP1 and TET2 protein. Logrank test was used to Univariate prognostic analysis. Cox regression model was used to multivariate prognostic analysis.Results1. Forty-one cases CMML patients included 27 male and 14 female cases. Among these cases,28 patients were classified as CMML-1, and 15 cases were diagnosed as CMML-2. Median WBC was 13.7X 109/L as patients were conf irmly diagnosed. Five patients had leukocytopenia (1.92-3.46×109/L). Median monocyte count in the peripheral blood was 2.13X109/L. All patients presented with bone marrow dysplasia, and most showed hyperplasia, except 3 cases. Abnormal chromosome was detected in 34% cases.2. We detected BAP1 and TET2 expression inbone marrow paraffin by immunohistochemistry from CMML and the control (IDA and AMML) patients, and found that 13 cases (31.7%) expressed BAP1,among CMML, including 20 cases in CMML-1 and 5 cases in CMML-2 Seventeen (41.5%) patients had TET2 positive inCMML-1 and eleven in CMML-2 For 40 cases of AMML, the expression of BAP1 occured in thirteen cases (32.5%), and the expression of TET2 was found in fourteen patients. From 20 cases of IDA, we found that the expression of BAP1 was one(5%), there is no expression of TET2(0%).The results showed that, there was no significant differences of BAP1 protein expression between the subtype of CMML-1 and CMML-2. The result revealed that BAP1 protein was highly express in CMML and AMML cases, respectively accounted for 31.7%,32.5%. But in IDA, it only expressed for 5%. We also found that TET2 protein was highly express in CMML and AMML cases, respectively accounted for 41.5%,35%. But in IDA,it did not express. There was no significant differences of BAP1 and TET2 protein expression between CMML and AMML. But comparison of BAP1 and TET2 protein expression in CMML, AMML, IDA patients were statistically significant difference. Aslo, comparision of BAP1 and TET2 protein expression between CMML plus AMML with IDA were statistically significant difference.3. Pearson correlation analysis showed no correlation between the expression of BAP1 protein and TET2 protein. And univariate analysis showed the expression of BAPl protein and TET2 protein have no relationship with CMML prognosis.4. It showed that median survival for CMML-1 and CMML-2 were 20 months and 12 months respectively, but there were no statistical significance of survival duration between them. Univariate analysis showed that age (> 60 yrs), neutrophil count (<2.0×109/L), lymphocyte count (<1.0×109/L), mature monocyte count (>5×109/L) and anemia (Hb<60g/L) were associated with poor prognosis for CMML. There was no statistical significance in subtype of CMML, LDH, gender, abnormal chromosome, CD16, HLA-DR, CD34, CD117, BAP1 protein, TET2 protein for overall survival. Only lymphocyte count and neutrophil count in peripheral blood were independent prognostic factors for CMML after multivariate analysis.ConclusionCMML mainly occur in elderly patients. Although most patients have leukocytosis and monocytosis at diagnosis, few case shows leucopenia and monocytopenia. Age, neutrophil, lymphocyte and monocyte count, severe anemia are associated with inferior prognosis of CMML. Lymphocyte< 1.0×109/L and neutrophil count<2.0×109/L are adversely independent prognostic factor for CMML. Different subtypes of CMML have no statistical significant in prognosis. The expression of BAP1 and TET2 protein have nothing to do with the prognostic of CMML.