| BACK GROUND Acute leukemia (acute leukemia, AL) is the major thre ats to human health as malignant blood diseases.Chemotherapy is one of the most effective and extensive treatments of acute leukemia.The phenomenon of multidrug resistance (MDR) during treatment process is the main factor to che motherapy failed. Axl is one of tyro sine kinases receptor family, which has be en isolated from the DNA of chronic myelogenous leukemia patients by the O ’Bryan[1].The geneis positioned in the19q13.1.It is about140KD molecule a cross the membrane. It is highly expressed in a wide variety of tumor tissues, such as lung cancer, thyroid carcinoma, stomach and colon cancer, esophageal, ovarian cancer, etc. In recent years long time of PI3K/AKT pathway activation has been found playing an important role for process and drug resistance in1eukemia. Currently the relationship between Axl and AKT in leukemia has not completely clear. They are differentially expressed in leukemia,which are expe cted to become detection, guiding treatment, and prognosis as molecular biolog y mark and new target treatment for acute leukemia.OBJECTIVE We determinate the Ax1,PAKT mRNA expression level of B MNCs in30treated first,12recurrent adult AML patients and9normal contr ols, preliminary analysis their roles in the occurrence and development of A ML,and discuss their relationships with drug-resistantMETHODS1. Bone marrow mononuclear cells from30newly diagnosed,12relapse/refractory AL (including AML and ALL) patients and9normal controls were analyzed, Real-time reverse transcription polymerase chain reaction (RQ-RT-PC R) was used to detect the expressions of Ax1、PAKT mRNA in bone marrow m ononuclear cells 2. All the statistical analyses were carried out using SPSS17.0. The sig nificance of different groups were evaluated by medians and P<0.05was consi dered statistically signigicant. levels of Ax1、PAKT mRNA expression between the two groups were compared by Mann-Whitney U Test, respectively.3. Spearman correlation coefficient was used to analyze the relevance bet ween Axl and PAKT mRNA.4. According to their response of chemotherapy, the newly diagnosed A ML patients was divided into two groups:complete remission group (CR) and non-complete remission group (PR+NR),5. Spearman correlation coefficient was used to analyze the relevance of Axl mRNA expression and clinical variables (including gender, age, peripheral WBC (white blood cell) counts,bone marrow blast percentage, chromosome karyotypes and immunophenotype). Spearman correlation coefficient was used t o analyze the relevance of PAKT mRNA expression and clinical variables (inclu ding gender, age, peripheral WBC (white blood cell) counts,bone marrow bias t percentage, chromosome karyotypes and immunophenotype).RESULTS1. The levels of Ax1mRNA expression in newly diagnosed group and rel apse/refractory group was higher than those in the control group (respectively Z=-3.133,P=0.002; Z=-3.695,P<0.001, P<0.05); The level of Axl mRNA express ion in Relapse/refractory group was higher than that in newly diagnosed group (Z=-2.924,P=0.003, P<0.05);2. The levels of AKT mRNA expression in newly diagnosed group and rel apse/refractory group are higher than those in the control group (respectively Z=-3.733, P<0.001; Z=-3.4825,P<0.001, P<0.05); The level of PAKT mRNA e xpression in Relapse/refractory group was higher than that in newl-y diagnosed group (Z=-2.032,P=0.042, P<0.05,)3. After two courses chemotherapy, the level of Axl mRNA was higher i n noncomplete remission group than that of complete remission group (Z=-2.908,P=0.004, P<0.05), the level of PAKTmRNA was higher in noncomplete rem ission group than that of complete remission group (Z=-2.767,P=0.006, P<0.05)4. In complete remission group, Axl mRNA and PAKT mRNA express-i on levels were positively correlated (r=0.595, P=0.003, P<0.05). In noncomp lete remission group, Axl mRNA and PAKT mRNA expression levels were po sitively correlated (r=0.762, P=0.028, P<0.05). In relapse/refractory patie nts, Axl mRNA and PAKT mRNA expression levels were positi-vely correlated (r=0.804, P<0.05)5. The expression level of Axl mRNA had no correlation with peripheral WBC counts,bone marrow blast percentage, gender, age, chromosome karyotye s and immunophenotype(P>0.05). The expression level of PAKT mRNA had n o correlation with peripheral WBC counts,bone marrow blast percentage, gende r, age, chromosome karyotypes and immunophenotype(P>0.05).CONCLUSIONS1. The levels of Axl mRNA expression in newly diagnosed group and re lapse/refractory group were higher than those in the control group. The level of Axl mRNA expression in Relapse/refractory group was higher than that in newly diagnosed group. Those results demonstrated that Axl was related to th e process of occurrence and development of AML2. The levels of PAKT mRNA expression in newly diagnosed group and relapse/refractory group were higher than those in the control group. The lev el of PAKT mRNA expression in Relapse/refractory group was higher than tha t in newly diagnosed group. Those results demonstrated that PAKT was relate d to the process of occurrence and development of AML3. The level of Axl mRNA was higher in noncomplete remission group than that of complete remission group, The lower the Axl mRNA expression1evel is, the higher the complete response rate is and the better clinical curati ve effect is.4. The level of PAKTmRNA was higher in noncomplete remission group than that of complete remission group. The lower the PAKT mRNA expressio n level is, the higher the complete response rate is and the better clinical cur ative effect is.5. The expression levels Axl and PAKT mRNA were positively correlate d in the complete remission groups, The expression levels Ax1and PAKT m RNA were positively correlated in the non-complete remission groups.The exp ression levels Axl and PAKT mRNA were positively correlated in the relapse/ refractactory AML groups.lt is demonstratethat Axl and PAKT mRNA maybe parti cipate in the onset, progress, drug-resistant of acute myeloid leukemia,and there may be some relativity in both action mechanism and clinical significance.6. The expression level of Axl mRNA had no correlation with peripheral WBC counts,bone marrow blast percentage, gender, age, chromosome karyoty pes and immunophenotype,which demonstrated Axl may be predictors independ ent these clinical characteristics. The expression level of PAKT mRNA had no correlation with peripheral WBC counts,bone marrow blast percentage, gender, age, chromosome karyotypes and immunophenotype, which demonstrated Axl may be predictors independent these clinical characteristics. |
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