الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia (AML) is agroup of clonal hematopoietic stem cell disorders in which both failure to differentiate and over proliferation of stem cell compartment results in accumulation of non functioning leukemic myeloblasts in bone marrow and blood. AML is the most common acute leukemia in adults, with a large variability as regard the clinical course, genetic and molecular basis.
Acute Myeloid Leukemia is a clinically and molecularly heterogeneous disease. Currently, cytogenetic findings provide the most important prognostic information and are used to guide risk-adapted treatment strategies.The identification of molecular markers that precisely differentiate a patient’s risk could improve treatment outcome, and deeply refine the prognosis of patients with AML.
Despite recent progress in diagnosis and management, AML still currently remains an incurable malignancy due to the presence of minimal residual disease (MRD). Previous studies have demonstrated that sensitive MRD detection could better estimate the total body burden of leukemic cells and allow for earlier therapeutic intervention prior to overt relapse, which would help to improve clinical outcome of patients with AML.
In 2003two new oncogenes were identified and were associated with human cervical cancer that are also overexpressed in other human tumors including those of gastrointestinal origin. The human cervical cancer oncogene (HCCR) is classified into two species, HCCR-1 and HCCR-2. (160)
Previous work suggests that cells expressing HCCR-1 and HCCR-2 are tumorigenic in nude mice. Their functional role in tumorigenesis may reside as a negative regulator of the p53 tumor suppressor gene. HCCR1- or HCCR2-transgenic nude mice could form spontaneous breast cancers, which further confirmed the critical role of HCCR in tumorigenesis.
(163)The aim of this study was to investigate the expression level of HCCR-1 m-RNA in patients with de novo AML, its relation to disease characteristics and its impact on prognosis.
This study was conducted during the period from January 1st 2015 till January 1st2017. A total of 35 patients presented to Hematology Department, Medical Research Institute, Alexandria University with denovo AML were included in the study and grouped according to the criteria revised by the French–American–British classification and followed up for one year.
The clinical findings in our patients were collected. The main presenting symptoms werefatigue, bone pain and bleeding.
Hemoglobin concentration (Hb)and platelet count showed statistical significant difference between the patients and control group. Blast % in AML patients ranged from 20 % to 88 %, mean value was 57.37 ± 19.83and a median of 56%.
Our AML patients were subclassified according to the French-American-British (FAB) classification system using morphologic, cytochemical criteria and immunophenotyping into AML subtypes. The most common type in our patients was M5 (37 %, 13 cases), followed by M4 (22.9 %, 8 cases), then M2 (20 %, 7 cases), then M1 (8.5%, 3 cases), M6 (8.5%, 3 cases) and lastly M7 representd by only one case. Liver enzymes (AST and ALT) were significantly higher in patients than in control group. While serum albumin was significantly higher in control group than in patients group. (p value <0.001). Blood urea, serum creatinine and serum uric acid were significantly higher in patients than in controls(p value <0.001), also LDH level was significantly higher in patients than in the control group.
The patients were treated according to the standard chemotherapy protocol for induction and they were followed up by bone marrow examination at day 28 to determine patient’s initial chemotherapy response whenever possible. Seven cases achieved CR after induction therapy (20 %). Nine cases attained partial remission (25.71%). Four cases achieved no response at all (11.4%).Thirteen cases died during one year of follow up (37.14%), Two of our patients were lost during the follow up (5.7%). The patients were followed up for one year. Two of our patients attained relapse during their follow up.
The mRNA levels of HCCR1 were quantified by real-time reverse transcription polymerase chain reaction in samples from 35 adult de novo AML patients and 10 healthy donors. The expressions of HCCR1 was significantly higher in patients with acute myeloid leukemia (AML) than those in healthy donors (P<0.001).However there was no significant difference between the expression levels of HCCR-1 preinduction and postinduction on day 28 in ten of our patients.
In the present study the relation between the HCCR-1 gene expression levels preinduction between died patients during induction therapy and those who survived postinduction showed statistical significant difference.
Further studies on a large scale of patients are required to ascertain whether HCCR-1 gene influences the long-term prognosis of patients, especially progression-free survival and overall survival.