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The Study on the Correlation between Sokal Staging and PTEN、BMI-1、BCR-ABL Gene Expression in Initial Chronic Myeloid Leukemia

Author: XiaLeiMing
Tutor: YangMingZhen
School: Anhui Medical University,
Course: Internal Medicine
Keywords: chronic myeloid leukemia Sokal stages study of correlating Prognostic gene
CLC: R733.72
Type: Master's thesis
Year: 2013
Downloads: 12
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Abstract


IntroductionChronic Myeloid Leukemia (CML) is a common one of the tumor proliferatingdisease，which generate from the multi-potential stem cell. Its incidence is about15%of the adult leukemia and it often occurs in the middle-aged people (range from45to55years old).At present, the commonly used evaluation of CML is the Sokcalintegration, which divided patients into three risk degree (high/middle/low).However,during the real clinic work, there often appears a difference between the degree andthe efficacy. Some latest research thinks that there are more than80%of CML patientin blast period has genetic alteration, except the Ph chromosome. Cortes believes theabnormal degree of the CML cell is highly related to the disease progression,especially the molecular abnormal detection of initial stage, which can guide theprognosis and the individualized detection in molecular level.Materials&MethodsCollect35primary treating patients since2011.10, who has diagnosed throughclinic, bone marrow swear and cytogenetic. Group them with the Sokal integration,9in high risk group,12in middle risk group,14in low risk group. Use the fluorescentquantitative PCR to detect the expression level of PTEN, BMI-1, BCR-ABL indifferent stage patient’s bone marrow. Analyze the correlation between the Sokal ResultsThere is no statistic significance of the expression of BMI-1、PTEN、BCR-ABLbetween the Sokal integration groups. The prognosis of each CML period (Sokalintegration) has no correlation with the expression of genes.ConclusionCML is more common when compared with other leukemia and the BCR-ABL isthe hottest and deepest researched gene. The displacement t (9;22) which leads to theBCR-ABL is now considered as the chromosomes level of cause of CML. The CMLcells’ product usually is the P210. It has the function that can enhance the activity oftyrosine kinase and change the tyrosine phosphorylation level of several proteins andthe function of microfibril actin. Then, the cell loss the reaction to the circumstanceand the apoptosis has been inhibited. Mus’ have found out that the developing ofCML through CP to AP has always accompanied with the rising of the mRNA levelof BCL-ABL. In the experiment, the CML AP patient’s expression of BCR-ABL inthe peripheral blood is the4.27times of the primary patient. And this result canindicate that the BCR-ABL may have played important role in the transition throughCP to AP. That is to say, the BCR-ABL is an index of unfavorable prognosis.PTEN is a high fidelity tumor suppressor gene. It can inhibit the enhancement oftumor, induce the apoptosis, depress the neoplasm invasiveness, blocking the cellcycle and control several apoptosis elements. It is believed that PTEN inhibit thegrowth, infiltration, invasion and transition. Pengs’ believed that the loss of PTENmay leads to the development of CML and in the stem cell of CML, the decrease ofPTEN gene may induces by BCR-ABL. The over-expression of it can slow down theprogression of CML and lengthen the life span of animal model. In addition, PTENcan inhibit the stem cell of leukemia and end its cell cycle. That is to say, the PTEN isan index of eusemia. BMI-1is one kind of the transcription factor of polycomb family genes. It isimportant in the regulation of normal cells and the leukemia stem cells and itsexpression may have relation with the malignance level. Mohtys’ research thinks theBMI-1may be the biomarker of the internal heterogeneity of CML and itsmeasurement can help judge the prognosis.Nowadays, it is still using two standards-Sokal and Hasford-in the clinical work.And the index of prognosis only has some simple one, like age, size of spleen andliver, peripheral blood and so on. There are no genes and chromosomes which haveconfirmed their correlation with prognosis. Along with the progress of moleculargenetics and the deeper understanding of pathogenesis, the former standard isincomplete. In real clinical work, there appears that some patients with good Sokalscore have been soon jumped into AP or have the resistance or insensitivity oftyrosine kinase inhibitors. It is a huge question that we can not make the accurateprognosis of CML, which can puzzle the selection of treatment protocols. Therefore,it is imperative to build a new overall and stable standard system. With the using ofnew technical method, large sum of changes in molecular level of tumor have beenfound and people understand this disease more exactly, which makes the explanationin molecular level of the variation between different diseases and the individualdifference with same disease possible. This new prognosis system which has built inthe genes and chromosomes level can classify the risk more accurate.This experiment group patient with Sokal integration, select the oncogene andanti-oncogene which has relation with prognosis. Then detect the expression of eachgene and analyze by the statistics analyzing software. We find that there is nodifference between each group which indicate that we can not distinguish patient’srisk in gene level by using Sokal integration.

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia > Chronic leukemia
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