Font Size: a A A

Proteomic Analysis Of Acute Leukemia Cells

Posted on:2005-11-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W CuiFull Text:PDF
GTID:1104360125950171Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Acute leukemia (AL) is a heterogeneous disease with distinct biological and prognostic groupings and the accurate classification is critical for treatment and prognosis. There are a cluster of alterations in the genotype and phenotye of the cells in the process of leukemogenesis. The transformed heamatopoietic cells in every developmental stage can form a distinct type of leukemia. Although the AL cells have the same morphological features, there is much difference at the molecular level of AL cells. Different types of AL have different prognosis and response to treatment. It is crucial to establish a new classification criteria that can reflect the leukemogenesis, the effects of treatment and prognosis. Only in this way, the patients with AL can get individual therapy, and gain complete remission.However, the current classification for AL cannot reflect the essential features of AL. With the introduction of French-American-British (FAB) classification in 1976, diagnosis and classification have been based on cytomorphology and cytochemistry, which provide the basis for the classification of AL into those arising from lymphoid precursors (acute lymphoid leukemia, ALL) or from myeloid precursors (acute myeloid leukemia, AML). But the correct rate is about 60-70%. It is hard to make diagnosis for some patients with AL. What's more, the classification made on the basis of morphology of AL cells cannot direct the clinical treatment. FAB classification was further solidified by the techniques of immunophenotyping, cytogenetics and molecular genetics, and has been improved over the past decades. The new classification combined the analysis of morphology, immunophenotyping, cytogenetics and molecular genetics of AL cells, has improved the accuracy of the diagnosis. For example, the immunophenotyping classification can distinguish the acute B-cell lymphocytic leukemia (ALL) from T-cell ALL. However, there are many cross-antigens among different subtypes of acute non-lymphocytic leukemia (ANLL). It is hard to make accurate diagnosis for ANLL. Although 80-90% AL patients have clonal cytogenetic abnormalities,only a few of AL patients have specific cytogenetic and molecular genetic abnormalities. In conclusion, the current leukemia classification remains imperfect and errors do occur. Moreover, no single test is currently sufficient for making the diagnosis. The current classification system cannot reflect the molecular characteristics, and cannot give instructions to make specific treatment according to different types of AL and different drug targets. To establish the classification system that can reflect the essential features of AL, hematologists have paid much attention to the study on the molecular features of AL. There are many studies at the level of mRNA(cDNA)to detect the genetic features of AL. However, the alterations of the genes cannot represent the alterations of proteins. The proteins are the direct executors for the physical and pathological activities. The alterations of proteins are the decisive factors in the process of disease. Therefore, the scheme based on the expression of protein in AL cells can reflect the essential features of the disease and lay basis for AL therapy. Although there are some progresses in the study of protein expression in AL, the study focused on one or several proteins. There are many events involved in leukemogensis. So it is crucial to understand the molecular features of AL cells comprehensively. With the accomplishment of the human genome project, the focus in biological science has transferred from genomic study to the proteomic study. The emergence of proteomics allows us to study the molecular features on a large scale for the first time. The main technology in proteome study includes 2-dimensional electrophoresis used to separate the proteins in the cells and mass spectrometry to identify the proteins. The proteomic profiling of human AL can facilitate diagnosing AL and understanding the mechanism of leukemogenesis, according to the type...
Keywords/Search Tags:Proteomic
PDF Full Text Request
Related items