الفهرس 
ACUTE MYELOID LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia describes a heterogenous group of hematological disorders characterized by a block in the terminal differentiation of a particular hematopoietic cell lineage. Cytogenetic and molecular assays have allowed patients’ follow up aiming for detection of minimal residual disease, prediction of patients’ outcome, in addition to providing the rationale for designing novel molecular-targeted therapeutic strategies.
Human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene is frequently amplified in human tumors, which indicates that the hTERT gene may be a target for amplification during the transformation of human malignancies including hematological malignancies. This genetic event has implications in diagnosis, prognosis and therapeutics of cancer.
In this regard, this study aimed to detect hTERT gene amplification in AML patients by FISH analysis and its relation to the standard prognostic factors.
In the current work, BM or PB samples were obtained from 21 adult AML patients, presented at the Hematology/Onclology Unit, Ain Shams University Hospitals. The patients were further divided into two groups; group I containing newly diagnosed AML patients and a relapsed case and group II containing patients taken at 28th day of chemotherapy.
All patients were subjected to complete history, thorough clinical examination and laboratory investigations including: complete hemogram, bone marrow aspiration with examination of Leishman-stained peripheral blood and bone marrow smears, immunophenotyping, karyotyping and detection of hTERT gene amplification using FISH technique.
The present study reveals positive hTERT gene amplification in 19/21 cases (90.5%) and negative amplification of hTERT gene (normal) in 2/21 cases (9.5%). The percent of amplification ranged from 3% to 76%. The No. of copies ranged from 2-9 copies per interphase cell.
The percent of amplification of hTERT gene is higher among poor outcome patients than good outcome; all patients with ≥ 20% of amplification associated with poor outcome, with highly statistically significant association. Also, we found that 10/13 of group I having ≥ 20% amplification and 6/8 (75%) of group II were associated with <20% of amplification with a statistically significant difference between them.
A highly statistically significant decrease in the PB blast % amoung patients with ≥ 20% amplification and a statistically significant decrease in the PLT count amoung patients with ≥ 20% amplification in comparison between patients with <20% of amplification.
Karyotyping of the encountered successful metaphases revealed normal karyotype in 7/16 cases (43.8%) and abnormal karyotype in 9/16 cases (56.2%); 5 cases (55.6%) showed structural aberrations, complex karyotype was detected in 1 case (11.1%) and numerical aberrations was detected in 3 cases (33.3%).
All favorable subgroup (4 cases) was associated with good outcome and the unfavorable (1 case) and 9/11 cases (81.8%) of the intermediate subgroup were associated with poor outcome with a statistically significant difference between both groups.
In conclusion, hTERT gene amplification was detected in AML; therefore telomerase can be a good cancer marker which may be involved in carcinogenesis of leukemia. Higher amplification was found in de novo cases than cases in remission which emphasise its role in clinical analysis, disease monitoring and detection of minimal residual disease.
It was correlated with poor patients’ outcome, indicating its negative impact on patients’ outcome and its potential as a promising target for therapeutic intervention. However, larger studies are needed to study its role as a prognostic marker.