Expression And Clinical Significance Of STAT5,SOCS1 And PTPRO In Leukemia

Objectives: Suppressor of cytokine signaling(SOCS)family is one of the negative feedback regulators of Janus kinase(JAK)–signal transducer and activator of transcription (STAT)signaling pathway.Many cytokines and growth factors transduct signal through JAK/STAT,(Janus kinase/signal transducers and activators of transcription) pathway, among which, JAK2 is most relative to hematopoiesis. STAT5 is the main downstream signal protein of JAK2, and been phosphorylated by JAK2,then dimerize and enter into the cell nucleus, thus regulating the transcription of relevant gene and supporting the growth,differention and proliferation of the cells. SOCS1 is an effective inhibitor of Jak catalytic activity.Leukemia is frequently associated with chromosomal abnormalities and oncogenic proteins forming, which activated signal transduction pathways involved in the survival and proliferation of the malignant cells. Among which, constitutive activation of JAK2-STAT5 by over expression or mutation was especially important to the malignant transformation of AML blasts. Pharmacologic inhibition of JAK2-STAT5,to abrogate AML cell proliferation may therefore represent an important part of targeted leukemia therapy.SOCS proteins are short-lived and ubiquitinated,and it is possible that they also work by targeting receptors and other signaling components for degradation. SOCS proteins have a similar structure:an N-terminal domain of variable length, a central Src homology-2 domain, and a C-terminal SOCS box. Biochemical and genetic studies have revealed that SOCS family members play an important role in the termination of cytokine and growth factor signaling.PTPRO is a member of the receptor-like PTPs, and was purified and cloned in the experiment screening the specifically expressed protein in the glomerular podocyte. PTPRO is highly conserved in the vertebrates from mouse to human. Human PTPRO is a member of the receptor-type protein tyrosine phosphatases(RPTPs). DNA hypermethy- lation-mediated silencing of PTPRO was reported in primary human tumors and cancer cell lines.In addition, PTPRO exhibits characteristics of a candidate tumor suppressor in human lung cancer.In this study,we investigated the expression of STAT5,SCOS1 and PTPRO cell in leukemia patients and normal controls, and Clinical Significance.Methods:The study enrolled 40 patients with acute leukemia(acute leukemia,AL) including 26 de novo AL and 14 CR patients. 15 cases of chronic myeloid leukemia(CML-CP) patients .10 healthy volunteers worked as normal control. 40 cases with acute leukemia(AL), 29 Acute myelocytic leukemia(AML)and 11 acute lymphocytic leukemia(ALL),according to FAB classification consist of,M11,M2 5,M3 15,M4 4,M5 3, M6 1,M7 0 and L1 3,L2 7,L3 1 respectively. There were 23 maleand 17 female patients with median age of 32.0 years(2-72 years). 15 cases of chronic myeloid leukemia patients included 9 males and 6 females with a median age of 42.0 years(20-65). 10 healthy volunteers worked as normal control,including 6 men and 4 women with a median age of 38.1 years(12-65 years). Quantitative reverse transcription-polymerase chain reaction(RT-PCR)was applied for STAT5, SOCS1 and PTPRO mRNA level monitoring in marrow in AL,CML patients and normal controls .Results:1 The expression of STAT5 in de novo AL patients were significantly higher than in CR patients(P=0.024)and nomal controls(P=0.000<0.001). The expression in CR patients were significantly higher than in nomal controls(P=0.000<0.001) and CML patients(P=0.000<0.001). The expression in CML patients were significantly higher than in nomal controls(P=0.000<0.001) ,but lower than in CR patients(P=0.000<0.001). There were no significant difference in ratio of the positive expression among ALL and AML groups in de novo AL patients (P=0.685).2 Ratio of the positive expression of SOCS1:The Ratio of the positive expression of SOCS1 in de novo AL patients and in CR patients were significantly lower than in nomal controls (P=0.000<0.001) .The expression in de novo AL patients were significantly lower than in CR patients (P=0.014). The expression in CML patients were significantly lower than in CR patients and nomal controls(P=0.000<0.001).There were no significant difference in CML patients and de novo AL patients .normal controls(P=0.109). There were no significant difference in ratio of the positive expression among ALL and AML groups in de novo AL patients (P=0.131).3 The expression of PTPRO in de novo AL patients were significantly lower than in nomal controls(P=0.000<0.001). The expression in de novo AL patients were significantly lower than in CR patients (P=0.028). The expression in CML patients were significantly lower than in CR patients (P=0.001)and nomal controls(P=0.000<0.001).There were no significant difference in CML patients and de novo AL patients (P=0.295). There were no significant difference in ratio of the positive expression among ALL and AML groups in de novo AL patients (P=0.158).4.1Ratio of the positive expression of STAT5/PTPRO: The expression in de novo AL patients were significantly higher than in CR patients(P=0.000<0.001) and nomal controls(P=0.000<0.001). The expression in CR patients were significantly higher than in nomal controls(P=0.005). The expression in CML patients were significantly lower than in de novo AL patients (P=0.001) and significantly higher than in nomal controls(P=0.000<0.001). There were no significant difference in CML patients and CR patients (P=0.237). The expression in AML patients were significantly higher than ALL patients (P=0.000<0.001) of de novo AL patients4.2Ratio of the positive expression of STAT5/SOCS1: The expression in de novo AL patients were significantly higher than in CR patients(P=0.000<0.001) and nomal controls(P=0.000<0.001). The expression in CR patients were significantly higher than in nomal controls(P=0.000<0.001). The expression in CML patients were significantly lower than in de novo AL patients (P=0.000<0.001) and significantly higher than in nomal controls(P=0.000<0.001). There were no significant difference in CML patients and CR patients (P=0.511). The expression in AML patients were significantly higher than ALL patients (P=0.000<0.001) of de novo AL patients5 The relationship between expression STAT5,SOCS1 and PTPRO mRNA level and gender. The 55 patients with leukemia including 31 males and 24 females . There were no significant difference in ratio of STAT5,SOCS1 and PTPRO mRNA level among those groups (P>0.05).6 The relationship between expression STAT5,SOCS1 and PTPRO mRNA level and age. The 55 patients with leukemia including 13 children and 42 adult. There were no significant difference in ratio of STAT5,SOCS1 and PTPRO mRNA level among those groups (P>0.05).Conclusions:1 We monitored higher expression of STAT5 in de novo AL patients and CML patients .its lower expression in CR patients,which indicated that the abnormal activation of JAK-STAT signaling pathway and the high expression of STAT5 may play a role in pathogenesis in acute leukemia and chronic myeloid leukemia patients.2 We monitored lower expression of SOCS1 in de novo AL and CML patients.It is suggested that the methylation of SOCS1 had close relationship with its lower expression and the silence of expression.There were no significant difference in CR patients and normal controls,which indicates that SOCS1 was one of anti-oncogene.3 We monitored lower expression of PTPRO in de novo AL patients and CML patients .its higherer expression in CR patients,which indicated that the low expression of PTPRO may play a role in pathogenesis in leukemia patients and that SOCS1 was one of anti-oncogene. 4 We monitored higher expression of STAT5/PTPRO and STAT5/SOCS1 in de novo AL and CML patients. its lower expression in CR patients, which indicated that the abnormal activation of oncogene and silencing of anti-oncogene may play a role in pathogenesis in acute leukemia.