Study On The Expression And Clinical Significance Of Flt-3 And C-kit Together With Their Ligands In Acute Leukemia

Objective: To explore the expression level of human flt-3(CD135)and c-kit (CD117) in acute leukemia(AL).The focus of the study will be laid on the value of flt-3 and c-kit expression in diagnosis for acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), Seeing the role of pathogenesis in AL. And the serum level of FL and SCF were also examined in AL patients, analyzing their clinical relationship. Methods: By comparison with 8 controls, 82 cases with acute leukemia patients at presentation (61 AML patients, 21 ALL patients ) were screened for flt-3 and c-kit on bone marrow mononuclear cell(BMMNC) by reverse transcription–polymerase chain reaction (RT-PCR). Enzyme linked immunosobent Assay (ELISA) was used to measure the serum level of FL and SCF respectively in initially diagnosed 27 cases of AML and 13 cases of ALL. Results: ⑴The expression of flt-3 and c-kit were negative in normal controls; abnormal flt-3 were highly expressed in 48 AML cases; 15 cases in ALL. No difference in AML and ALL before chemotherapy, but they all have significantly difference compared with health individuals. After chemotherapy the expression of flt-3 reduced in AL, positive flt-3 in AML were 8 cases, while 3 in ALL. There have obviously difference in AL fore-and-aft chemotherapy. The subtypes of AML have no clearly relationship with flt-3 expression level. ⑵The expression level of c-kit were detected in patients with AML were 20 cases, and 2 in ALL, c-kit in AML clearly higher than those of healthy individuals and those of patients with ALL. After treatment, positive c-kit in AML were 3 cases, no one in ALL. Between c-kit and subtype of AML have a certain extent relationship, M2 expression level were tiptop, secondly M3 , finally M4 and M1. ⑶flt-3 and c-kit co-expressed in AML and ALL were 16 cases, most of them attending by abnormal chromosome complexity. The serum average level of SCF in controls were 97.28±12.99 pg/ml. AML were 426.58±32.55 pg/ml before therapy; after treatment, the serum level of SCF declined to 169.82±18.51 pg/ml. 79.43±10.56 pg/ml in ALL before therapy, while after treatment were 63.09±10.43 pg/ml. The serum level of SCF in ALL similared with controls. ⑷Before treatment, the serum FL average level in controls were 15.25 ±5.62 pg/ml, the serum FL level in AML fore-and-aft were 15.94±2.39 pg/ml and 19.93±3.47 pg/ml;the level of FL in ALL fore-and-aft were 23.63±6.66 pg/ml and 20.47±3.49 pg/ml. The serum level of FL have no difference in AL before therapy contrasted with normal controls, and the same with treatment. Conclusion: ⑴Flt-3 is widely expressed in AML and some cases of ALL , can not distinguish AML and ALL commendably. C-kit mostly expressed in AML, few in ALL. The expression of c-kit in M2 were most, next M3 while M4 and M1 in AML were lowest. There is no consistence between the expression level of c-kit and subtypes of AML, which can be considered as a indicator for diagnosis of AML, distinguish with ALL and can help to classify the subtype of AML. ⑵The serum SCF level in patients at presentation AML were higher than controls. after sick achieved CR, the level of SCF reduced. The serum level of SCF in ALL patients and controls have no clearly difference. ⑶The serum level of FL in AL patients have no obviously difference compared with controls, whether or not therapy.⑷The expression level of flt-3 and c-kit correlated to abnormal karyotype and rate of CR, independent of peripheral white blood cell number, blast cell in bone marrow, hepatomegaly and splenomegaly.