- Molecular analysis of acute myeloid leukemia
- Introduction
- Various changes in the hematopoietic progenitor’s cells and the accumulation of the acquired genetic alteration have led to the development of the acute myeloid leukemia (AML). Studies have shown that most of the patient nowadays with AML has at least 1 chromosome aberration in their marrow blast. There are also multiple submicroscopic genetic alterations with prognostic significance that have been discovered. This article review mainly focus on first establishing the constitution of normal karyotype in the AML. In addition, the review also provides the genetic alterations that are clinically as both the prognostic marker and the various potential targets for the risk-adapted therapy. In relation to this the article first analyses the internal tandem duplication (ITD) of the FLT3 gene, which is one of the most important prognostic factor. In addition the article also analyses other prognostic factors that have been reported in various studies.
- Importance of determining the patient karyotype is truly normal
- Studies have shown that the older patients have a high level of de novo cytogenetic normal (CN). It is also evident that CN AML has a varied range of between 40% to 49% in adult. The cytogenetically crone is normally detected in the cells cultured in vitro for 24 to 48 hours. However, the blood spacemen can sometimes be cryogenically normal, even in the case where the marrow is abnormal. In order to eliminate such cases it is important to ensure that the blood analyzed constitute of 20 metaphase cells from marrow sample that has been culture in 24hours. One of the major importances of determining the patient karyotype is to establish and categorize their genetic makeup in order to facilitate the treatment.
- Mutation of the FSM-related tyrosine kinase
- One of the earliest genetic alteration recorded mainly involved the internal tandem duplication (ITD) in the juxtamembrane domain of the FLT3gene. This gene is believed to encode for the member of class III receptor tyrosine kinase family that is normally expressed on the surface of the bone marrow (BM) of hematopoietic progenitor cells. This FLT3 gene has shown considerable genetic abnormalities. In clinical studies the CN AML patient who carry this gene are different from those without FLT3-ITD in relation to the pretreatment characteristics and the various treatment outcome.
- Partial tandem duplication (PDT) of the myeloid/ lymphoid or mixed lineage leukemia (MLL)
- The MLL-PTD is also known to affect the prognosis in CN AML patient. Studies indicate that MLL-PTD occurs approximately in 8% of all the CN AML patients. The condition normally involves the duplication of a genomic region spanning exon 5 through11. In addition the MLL-PDT may also involve the duplication of the region into intron 4 of MLL gene. It is worth noting that the preclinical characteristic of the CN patient with MLL-PTD do not differ with those without.
- Over expression of the BAALC gene
- Studies have shown that the gene is normally expressed in the neureoectodermal tissues and the precursor of the hematopoietic tissues where they encode for protein, which are not similar to any of the known proteins. High expression of the gene is detected in the patient with AML. In addition it is also worth noting that the patient who were found to have high levels of FLT3 gene also have a high level of this type of gene.
- Mutation of the CAAT /enhancer-binding protein α (CEBPA) gene
- This type of gene normally encode of the family basic leucine zipper transcription, which plays an important role in the granulopoiesis. The study of CEPPA gene mutation has helped to provide prognostic information on that is already provided by the MLL-PTD and FLT3-ITD on age and other factors related to AML.
- Over expression of the ETS-related gene (EGR) and other prognostic factors in
- This over expression of the ETS related gene has also been discovered in the AML patients. This therefore implies that it might be used to detect the adverse prognosis in CN AML patients. However, the recent study by Dohner indicated that almost a quarter of the patient did not carry the FLT3-ITD, FLT3-TKD, MLL-PTD or mutation in the CEBPA. This clearly indicates that there is need for the study to be established to establish a gene mutation that has a significant prognostic factor.
- Conclusion
- From the above it is evident that the gene expression profiling can be used to separate the cytogenetically normal AML patient into prognostic subgroups. Some of the microscopic genetic alteration have been discovered which include the BAALC and CEBPA genes. However, it is also worth noting that there is need for a research to be carried out to establish a gene mutation that has a prognostic factor. This can help to ensure that there is selection of the appropriate treatment method to be used on the AML patients.
- Reference
- Mrózek,K.et, el.2007 clinical reverence of mutation and gene expression changes in adult acute myeloid leukemia with normal cytogenetic are we ready for a prognostically molecular classificationy. New York. American society of hematology.
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