The Expression And Clinical Significance Of JAK2, SOCS1, SOCS2 And SHP-1 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. In this study, we investigated the expression of JAK2 SOCS1 SOCS2 and hematopoietic cell phosphatase(SHP-1) in leukemia patients and normal controls, and explored their role in the pathogenesis of leukemia.Methods: The study enrolled 62 patients with acute leukemia (acute leukemia, AL)including 36 de novo AL and 26 CR patients. 50 cases with Acute myelocytic leukemia(AML) and 12 acute lymphocytic leukemia(ALL), according to FAB classification consist of M1 1, M2 12, M3 18, M4 12, M5 6, M6 1, and L1 1, L2 10, L3 1respectively. There were 32 male and 30 female patients with median age of 31.5 years (16-79 years). 23 cases of chronic myeloid leukemia patients included 11 males and 12 females with a median age of 38 years (14-73). 19 healthy volunteers worked as normal control, including 11 men and 8 women with a median age of 38 years (18-52 years). Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was applied for JAK2, SOCS1, SOCS2 mRNA level monitoring in marrow in AL, CML patients and normal controls and quantitative RT-PCR for SHP-1 mRNA level monitoring.Results:1 There were no significant difference in ratio of the positive expression of JAK2 among those groups.2 The expression of JAK2 in de novo AL patients were significantly higher than in CR patients(P=0.0001) and nomal controls(P=0.0014). There were no significant difference in CR patients and nomal controls(P=0.1734). The expression in CML patients were significantly higher than in nomal controls(P=0.041), but lower than in de novo AL patients(P=0.037). The expression of JAK2 in AML patients were significantly higher than in ALL patients (P=0.0099).3 Ratio of the positive expression of SOCS1: The Ratio of the positive expression of SOCS1 in de novo AL patients were significantly lower than in CR patients (χ2=4.761 P=0.029) and in normal controls(χ2=9.131 P=0.003). There were no significant difference in CR patients and normal controls(χ2=0.525 P=0.517). There were no significant difference in de novo AL patients and CML patients(χ2=0.646 P=0.422).4 The expression of SOCS1 in de novo AL patients were significantly lower than in nomal controls(P=0.0054) and CR patients(P=0.012). There were no significant difference in CR patients and nomal controls(P=0.146). The expression in CML patients were significantly lower than in nomal controls(P=0.031).5 There were no significant difference in expression of SOCS2 among those groups .6 Ratio of the positive expression of SHP-1: The Ratio of the positive expression of SHP-1 in de novo AL patients were significantly lower than in CR patients(χ2=19.578 P=0.001), and significantly higher than in normal controls(χ2=17.929 P=0.001). The CML patients were significantly lower than in nomal controls(χ2=13.878 P=0.001<0.01).7 The expression of SHP-1 in de novo AL patients were significantly lower than in CR patients and nomal controls (p=0.00). The expression in CML patients were significantly lower than in nomal controls(P=0.00).8 There were no significant difference in CR rate during first course of treatment among those groups(JAK2+ and JAK2-; SOCS1+ and SOCS1-; SOCS2+ and SOCS2-; SOCS1-SOCS2 - and SOCS1+SOCS2 +; SHP-1+SOCS2+and SHP-1-SOCS2-). But the CR rate in SHP-1+ groups were significantly higher than that in SHP-1- groups, and the CR rate in SHP-1+SOCS1+ groups were significantly higher than in SHP-1-SOCS1- groups.Conclusions:1 We monitored higher expression of JAK2 in de novo AL patients and its lower expression in CR patients, which indicated that the abnormal activation of JAK-STAT signaling pathway and the high expression of JAK2 may play a role in pathogenesis in acute leukemia.2 The expression of JAK2 in AML patients were significantly different from which in ALL patients, which suggests that the approach by which they activate JAK-STAT signaling pathway was different. This will help us explore their pathogenesis respectively.3 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.4 Suppressor of cytokine signaling (SOCS) family are one kind of the negative feedback regulators of JAK-STAT signaling pathway. The SOCS family are regulated by many cytokines. The negative regulation of JAK-STAT signaling pathway is a common consequence of functions of SOCS family members. SOCS2 may be a member with relatively weak role among them. So there were no significant difference in expression of SOCS2 among those groups.5 We monitored lower expression of SHP-1 in de novo AL patients and higher expression in CR patients. The methylation of SHP-1 is Considered to be closely related to its low expression and deficiencies. Lower expression of SHP-1 was correlated with lower CR rate, which indicates SHP-1 had close relationship with the prognosis of leukemia patients. SHP-1 can be used as prognostic indicators in leukemia.