الفهرس 
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Abstract
The acute leukemias are a heterogenous group of neoplasms that affect
hemopoietic stem cells. They are broadly classified into acute myeloid leukemia
(AML) and acute lymphoid leukemia (ALL) based on the cell of origin. Leukemia
accounts for some 300,000 new cases each year (2.8% of all new cancer cases)
and 222,000 deaths. This rather high ratio of deaths / cases (74%) reflects the poor
prognosis of leukemia in many parts of the world.
AML and adult-onset ALL are aggressive diseases with generally poor prognoses. The primary cause of treatment failures in patients with these diseases is the emergence of multidrug resistance mostly due to defects in apoptotic pathways. The initial leukocyte count and age at diagnosis have traditionally provided the most reliable basis for patient stratification; this is because these parameters are readily available and are relatively independent predictors of prognosis. The immunophenotype and cytogenetic abnormalities of leukemic cells are also important prognostic factors.
As a result of the accumulation of knowledge on the molecular biology of malignancies, new diagnostic modalities are beginning to be incorporated into diagnostic, prognostic and therapeutic strategies. If specific patterns of gene expression can be correlated with clinical features in AML and ALL, a refinement of current prognosis-based stratification systems would be possible.
Summary and Conclusions
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Recent progress in the use of DNA microarrays has identified genes that regulate cell cycle control, DNA repair, and apoptosis which may also participate in disordered cell proliferation and cancer progression in leukemia. Alterations in the basal level of expression of these genes may also affect the drug response and clinical outcome of leukemic patients. The identification of such new gene markers is therefore important not only to gain a basic understanding of the signaling pathways that operate in leukemogenesis, but also to implement enhancements to disease classification systems and to productively target disease with novel therapies.
Therefore, the current study was designed to evaluate the expression of livin, a member of the inhibitor of apoptosis family proteins (IAP) family in adult AML and ALL to investigate a possible relation between livin expression and the clinical features at diagnosis, prognosis and treatment outcomes and therefore determine the potential role of livin expression as a prognostic marker in order to achieve a more refine risk-oriented treatment stratification with intensification of therapy in those patients prone to resistance and/or relapse.
In order to fulfill our aim, this study was conducted on 46 subjects divided into the following three groups:
a) Control group:consisted of 12 healthy adult volunteers (6 males and 6 females).
b) ALL group: consisted of 16 patients (6males and 10 females).
c) AML group: consisted of 18 patients (6 males and 12 females).
Summary and Conclusions
115
Complete medical history was taken from all subjects, abdominal ultrasound was done for ALL and control groups and periferal blood (PB) samples (8-10 ml) were collected from all subjects for the determination of:
1- Serum albumin and surface markers: CD13, CD34, HLA-DR for AML and control groups.
2- Hemoglobin concentration (Hb) and Platlet count for ALL and control groups.
3- White blood cell count (WBCs), serum lactate dehydrogese (LDH), cytogenetics, immunophenotyping and livin expression for AML, ALL and control groups.
Then statistical analysis was done for these parameters to gain more insight into our results.
* The results of the current study are summarized as follows:
(1) Significantly lowered levels of serum albumin and significant higher expression of the surface markers CD 13 and HLA-DR were observed in AML group as compared to the control group.
(2) The liver size and the spleen size were significantly higher and the Hb concentration and the platlet count were found to be significantly lower in the ALL group as compared to the control group.
(3) As for the main target of the current study, livin expression was found to be significantly higher in the AML and ALL groups when compared to the control
Summary and Conclusions
116
group supporting its antiapoptotic role in tumor initiation and progression. Also, the expression level of livin in ALL group is significantly higher than in AML group which may be attributed to the difference in the genetic aberrations leading to leukemogenesis in the 2 types suggesting that livin plays different roles in the pathogenesis of both types.
(4) In AML group, the livin expression level was significantly higher in HLA-DR+ and CD13 − than HLA-DR− and CD13 + AML patients while there was no significant difference in the livin expression level between CD34+ and CD34− AML patients which implies that CD34 expression on AML blasts does not play per se a prognostic role, but could influence clinical outcome when associated with some genetic lesions and/or chromosome aberrations. Also, livin expression level was significantly negatively correlated with serum albumin level indicating the poor clinical state of the patients as it is considered as a poor prognostic factor.
(5) In ALL group, livin expression levels were significantly higher in male patients compared with female patients.
(6) Livin expression was significantly higher in adult AML and ALL with unfavorable prognosis at diagnosis. In addition, high livin expression was significantly negatively correlated with event free survival (EFS) and overall survival (OS) in both groups. This suggests that livin expression is a potential independent unfavorable prognostic marker in both types of acute leukemia.