Expression of β-catenin Gene in Human Hematopoietic Cell Lines and Leukemia Patients.

It has been well known that altered expression of β-catenin is an important event in the genesis of a number of solid malignancies. But to date little is known about its exact gene expression level in hematologic malignancies. In this current study we firstly detected the expression level of β-catenin in several hematopoietic cell lines. β-catenin mRNA was expressed in all hematopoietic cell lines tested. U937, K562, KG1a and HEL cells showed high expression level; Jurkat, Namalwa, Roumas, Raji, Daudi cells showed moderate expression level; while LCL-H, HL-60 and NB4 cells expressed only low level of β-catenin mRNA. In accordance with what we saw in RT-PCR, the results of ABC immunohistochemistry revealed that β-catenin was expressed widely in all cell lines tested though in various degree. We then detected and analyzed the expression of β-catenin in primary leukemia cells. One hundred and twenty-five patients with de novo leukemia from our hospital were studied after receiving informed consent, including 70 acute myeloid leukemia(AML), 28 acute lymphoid leukemia(ALL), and 27 chronic myeloid leukemia(CML), among of them 18 were in chronic phase (CP), 4 were in accelerated phase (AP) and 5 were on blast crisis (BC). The median age of the patients was 31 years old (3–68 years old), 71 were males, and 54 were females. Bone marrows MNCs from 23 healthy donors with a median age of 34 were used as controls for β-catenin expression at the same time. The results showed that the total expression level of β-catenin mRNA in acute leukemia group was significantly higher than that in normal bone marrow (p<0.005) and also higher than 18 patients in CML-CP (p<0.001). However it failed to show statistic significance between patients in CML-CP and normal donors (p>0.05). Though there is no difference between AML and ALL(p>0.05), either the expression level of β-catenin in AML group or that in ALL group was statistically higher than that in normal donors (p=0.005 and 0.032 respectively) and that in CML-CP(p=0.002 and p<0.001). However compared the level of 4 patients in CML-BC and 5 patients in CML-AP with that of 18 patients in CML-CP, a statistical difference (p=0.03) could be seen. As 70 AML cases (aged from 3 to 68 years old, with median age of 31; 42 males and 28 females) were further classified as M1 to M6 subtypes according to FAB criteria, the level of β-catenin in M2 (23 patients), M3 (18 patients), M4 (12 patients,), M5 (13 patients) sub-groups were significantly higher than that in normal (p<0.001, p=0.004, p=0.001, p=0.01, respectively). But there were no differences within these groups. The level for M1 (2 cases) and M6 (1 cases) sub-groups failed to show statistic difference with normal donors because of low number case. Some studies indicated that β-catenin is a strong and independent prognostic marker in some types of solid tumors. However, in the presented study no significant relationship was observed between over expression of β-catenin and clinical index such as age, initial WBC number, unfavorable cytogenetic abnormalities, and therapy responses. Our study provides strong evidence that there exists an overexpression of β-catenin in both of AML and ALL cells but not in CML-CP. However its clinical significance is to be further evaluated.