الفهرس 
ACUTE MYELOID LEUKAEMIAOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukaemia is a rapidly progressing extremely heterogeneous haematological disorder. Novel cytogenetic and molecular aberrations are continuously being identified in AML patients which have direct impact on patients’ prognostic outcome.
The incidence of abnormal karyotypes in AML has been reported to be 55% to 78% in adults and 77% to 85% in children which could be detected by conventional cytogenetic techniques. However, still a proportion of patients show an apparently normal karyotype at presentation which might harbour leukaemia - associated gene fusions below the level of resolution of detection by G- band karyotyping or even unable to be detected by conventional methods as AI where FISH studies and SNP Microarray Gene Chips aid in the diagnosis of this subset of patients.
The present work aimed at identifying AI and any additional copy number gains/losses which is considered as a novel aberration that lies beyond the resolution of the karyotype and assess the clinical prognostic outcome of those patients.
We studied 52 AML patients, 26 males and 26 females (ratio 1:1), age ranged from 7 months to 77 years using conventional G-band karyotyping followed by running them on 250K SNP Microarray Gene Chips then the final array results were confirmed by FISH studies.
Karyotyping results showed numerical abnormalities in 12 (23%) of patients, structural abnormalities in 27 (52%) of patients and normal karyotype in 20 (38%) of patients with only one case who’s culture failed. Patients’ results were further classified into different cytogenetic risk categories with the majority falling within the intermediate risk group.
Whole Genome Wide analysis revealed areas of AI spanning around the telomeric ends of various chromosomes in five adults out of fifty two patients studied (10%), involving chromosomes 4q (1/5), 6p (1/5), 13q (1/5) and 12p (2/5) and ranging from 11Mb-80Mb. Three out of the five patients (60%) were males, three patients (60%) were M1 FAB subtype and three patients (60%) had normal karyotype. FISH using specific probes confirmed normal copy number of these regions verifying that they resulted from somatic recombination event without any loss or gain of chromosomal material and also revealed a cryptic t(11;12) associated with an area of CNN-LOH of 12p in one case.
Moreover, we identified areas of additional copy number gains/losses in relation to the karyotype in 12(23%) out of the fifty two patients. FISH using targeted specific probes confirmed microarray results in only 5/12 (42%) of patients which could be attributed to software bias and that not all areas of query duplications/deletions are a true image of the patient’s copy number state and also revealed a cryptic t(5;17),t(9;17) associated with p53 and p16 gene deletions in one case.
Regarding the clinical outcome of the studied patients, all patients falling within the favorable cytogenetic risk group and twenty two out of the thirty six cases falling within the intermediate risk group showed clinical remission, while six cases within the intermediate risk group passed in relapse and eight cases of the same group died. All cases within the adverse risk group had died.
As regards the five patients showing AI, two died shortly after presentation despite falling within the intermediate risk group, while one patient had relapsed and two patients were alive and well.