Expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia and their significances / 白血病·淋巴瘤

ABSTRACT

Objective To investigate the expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia (CMML) and their relationship with the prognosis of CMML. Methods The bone marrow paraffin specimens of 41 cases from 41 adult CMML patients diagnosed by Shanghai Sino-US Joint Leukemia Coordination Group from September 2003 to May 2007 were collected. The immunohistochemistry was used to detect the expressions of BAP1 and TET2 proteins in 41 CMML patients. The expressions of TET2 and BAP1 proteins were also detected by the same method in 40 adult patients with acute myelomonocytic leukemia (AMML) and 20 patients with iron deficiency anemia (IDA) diagnosed at the same time as the comparison. The clinical data of 41 CMML patients were analyzed by using retrospective cohort study. The count data were compared by using chi-square test. The correlation between expressions of BAP1 and TET2 proteins was analyzed by using Pearson correlation analysis. Kaplan-Meier method was used to calculate the survival time, and Log-rank test was used for single factor analysis. Results In 41 CMML patients, the positive expression rate of BAP1 was 31.7％ (13/41), including 28.6％ (8/28) in CMML-1 patients and 38.5％ (5/13) in CMML-2 patients; the positive expression rate of TET2 was 41.5％ (17/41), including 39.3％ (11/28) in CMML-1 patients and 46.2％ (6/13) in CMML-2 patients. In 40 AMML patients, the positive expression rate of BAP1 was 32.5％ (13/40), and the positive expression rate of TET2 was 35.0％ (14/40). In 20 IDA patients, the positive expression rate of BAP1 was 5.0％ (1/20), and TET2 had no positive expression. There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML-1 and CMML-2 patients (χ 2 = 0.40, P = 0.53; χ 2 = 0.17, P = 0.68). There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML and AMML patients (χ 2 = 0.01, P = 0.94; χ 2 = 0.36, P = 0.64). There were significant differences in the positive expression rate of BAP1 and TET2 proteins between hematological neoplastic disease (CMML+AMML) and hematological non-neoplastic disease (IDA) (χ 2 = 6.01, P < 0.05; χ 2 = 11.04, P < 0.01). Pearson correlation analysis showed that there was no correlation between expressions of BAP1 and TET2 proteins (r = 0.35, P = 0.27). Univariate analysis showed that anemia (Hb < 60 g/L), mature monocyte count ≥ 2.0×109/L, neutrophil count (1.5×109/L), abnormal karyotype were associated with poor prognosis for CMML. Protein expressions of BAP1 and TET2 were not related with the prognosis of CMML (χ 2 = 0.28, P = 0.600; χ 2 = 0.53, P = 0.460). Conclusion Both BAP1 and TET2 proteins have high positive expression rates in CMML patients, but the expressions of them are not related to the prognosis.