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Abstract The aim of this study was to assess the level of expression of Aspartate BetaHydroxylase (ASPH) in serum of Egyptian AML patients and study its clinical significance. The study included 30 AML patients and 10 healthy control subjects. The patients were recruited from attendants of the Clinical Hematology and Oncology Unit, Internal Medicine Department, Ain Shams University during the period from August 2019 to March 2020. Patients were included if were aged 16 years and have newly diagnosed AML. AML patients were subjected to full history taking, thorough clinical examination and routine investigations including complete blood count, kidney and liver function tests, LDH, and coagulation profile. Bone marrow aspiration was done for morphologic examination and cytogenetic and molecular studies. Immunophenotyping was done by immunohistochemistry or flowcytometry. Radiographic studies were done for assessment of extramedullary disease. Cerebrospinal fluid examination was done in cases of FAB M4-5 subtypes or if signs of CNS infiltration existed. Measurement of human Aspartyl/Asparaginyl Beta-hydroxylase level (ASPH) in serum using ELISA Kit in patients at time of diagnosis and in the ten healthy persons. The patients’ status were assessed at day 28 for remission state in response to induction therapy with the combination of 3+7 regimen. Only one patient relapsed till the end of the study from the remitted alive patients.The results of the study demonstated significantly higher ASPH level in the AML group compared to the control group (p < 0.001). The median level of serum ASPH was 105 ng/L (range: 55-540 ng/L) in the AML group versus 40 ng/L (range: 20-50 ng/L) in the Control group. The majority of the AML patients had M2 FAB class, and 6 patients were M4 class. Four patients had secondary AML. The majority of the AML patients (n=24) had normal cytogenetics. FLT3 was found in 7 of the AML patients (23.3%). Extramedullary disease at diagnosis was found in 19 patients. None of the AML patients had CNS infiltration. Cytogenetic risk classification was as follows: high (n=9, 30.0%), intermediate (n=19, 63.3%), and low (n=2, 6.7%). Eight patients (26.7%) were resistant to induction therapy at day 28, while the remaining 22 (73.3%) were in remission. Only one patient relapsed till the end of the study from the remitted alive patients. One of the resistant patients died during the follow up. After induction therapy, 16 out of the 19 patients (84.2%) with intermediate cytogenetic risk turned to be low risk, while 3 (15.8%) became high risk. High expression of serum ASPH did not show a clear association with clinical and laboratory prognostic factors in AML patients. There was no apparent trend in the serum levels of ASPH in relation to the FAB classification. There was no significant difference between M1+M2 and M4+M5 subcategories (p = 0.427). There was no significant difference in the serum level of ASPH between patients with extramedullary disease and those without (p = 0.449). There was no significant difference between patients with normal and abnormal cytogenetics in the level of serum ASPH (p = 0.651). Apparently, there was a trend of increasing serum of ASPH with increasing cytogenetic risk, however, there was no significant difference between patients with high risk and those with low or intermediate cytogenetic risk in the level of serum ASPH (p = 0.304). Patients with mutant FLT3 had higher serum ASPH compared to those with wild FLT3 with a trend towards statistical significance (p = 0.084). There was no significant difference between patients with remission and those resistant to induction therapy at day 28 in the level of serum ASPH (p = 0.344). There was no correlation between serum levels of ASPH with total leukocytic count, blasts in peripheral blood or bone marrow, and serum lactic acid dehydrogenase level. |