ABSTRACT
Background@#Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children.Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated. In this study, we examined the expression of these genes in ALL patients (early pre-B-ALL and pre-B-ALL) and compared them with normal samples. @*Methods@#Bone marrow samples were collected from 40 patients (aged 0‒19 yr) newly diagnosed with early pre-B-ALL or pre-B-ALL using molecular and flow cytometric tests and from 15 control individuals. For molecular tests, RNA extraction and cDNA synthesis were performed, and Ang1, Ang2, Ang4, Tie1, and Tie2 gene expression was examined by real-time polymerase chain reaction. @*Results@#Ang2, Tie1, and Tie2 gene expression were significantly increased in patients with ALL, whereas Ang1 gene expression was decreased. The Ang4 gene did not show significant expression changes between the two groups. @*Conclusion@#Changes in the expression of the Ang-Tie system indicate a possible role of angiogenesis in ALL prognosis. Moreover, such changes can be considered as potential diagnostic biomarkers or therapeutic targets.
ABSTRACT
Background@#Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children.Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated. In this study, we examined the expression of these genes in ALL patients (early pre-B-ALL and pre-B-ALL) and compared them with normal samples. @*Methods@#Bone marrow samples were collected from 40 patients (aged 0‒19 yr) newly diagnosed with early pre-B-ALL or pre-B-ALL using molecular and flow cytometric tests and from 15 control individuals. For molecular tests, RNA extraction and cDNA synthesis were performed, and Ang1, Ang2, Ang4, Tie1, and Tie2 gene expression was examined by real-time polymerase chain reaction. @*Results@#Ang2, Tie1, and Tie2 gene expression were significantly increased in patients with ALL, whereas Ang1 gene expression was decreased. The Ang4 gene did not show significant expression changes between the two groups. @*Conclusion@#Changes in the expression of the Ang-Tie system indicate a possible role of angiogenesis in ALL prognosis. Moreover, such changes can be considered as potential diagnostic biomarkers or therapeutic targets.
ABSTRACT
Objective: Growth factor independence 1 (GFI1), a transcriptional repressor, is required for hematopoietic stem cell maintenance and self-renewal in addition to controlling differentiation and proliferation of myeloid cells. As murine studies have demonstrated that this transcription factor has a notable role in the initiation and progression of acute myeloid leukemia (AML) disease, the aim of the current study was to investigate and review the influence of GFI1 in human AML cells. Methods: GFI1 expression levels were measured by means of real-time polymerase chain reaction in 96 primary AML samples which were then compared to gene expression levels observed in 18 healthy subjects. Moreover, GFI1 expression patterns were analyzed based on specific AML subtypes including acute promyelocytic leukemia (APL). Finally, leukemic cells were stained to measure levels of myeloperoxidase (MPO) activity. Results: This study reports that AML patients have significantly higher GFI1 mRNA levels in comparison to healthy subjects and that, when considering AML subtypes, patients with APL have higher GFI1 expression than non-APL patients. Conclusion: It is also concluded that GFI1 overexpression in patients with high MPO levels, such as those of the APL subtype, is correlated with favorable disease prognosis as supported by other studies which demonstrate that increased peroxide activity and GFI1 are independently correlated with a favorable prognosis
ABSTRACT
P53 and AML1are two important tumor suppressor genes in regulation of hematopoiesis with a critical role in keeping balance between proliferation and differentiation. Alternations in the expression of these genes can be resulted in malignancy. The present study investigated the expression levels of P53 and AML1 genes in 82 de novo AML patient specimens against 12 normal control group using Real-Time-PCR. The results presented in this study revealed that AML1 gene expression was significantly higher and P53 gene expression levels was significantly lower in patients with AML in comparison with the normal control group [P = 0.016 and P = 0.002]. Furthermore, the correlation between P53 and AML1 was significant and positive [P= 0.037 and r= 0.231]. The lower levels of P53 expression were expected and in line with the normal role of this gene as a tumor suppressor gene, however AML1 over expression was in contrast with of its well known role in myeloid maturation. However, this findings suggest that despite the current established role this genes in myeloid cell differentiation, oncogenic form of AML1 [AML1a] has possibly increased and high expression of this isoform may act as an inhibitor for other normal AML1 isoforms and P53 as well
ABSTRACT
Nowadays, cord blood Hematopoietic stem cells [HSCs] are known as a valuable source for bone marrow transplantation but unfortunately their insufficient number is a limiting factor for using them in adult bone marrow transplantation. Cord blood HCSs expansion is an approach to overcome this problem, by inducing their self-renewal. TGF-b signaling pathway is a key inhibitory agent for HSCs self-renewal. In this study, we tried to enhance self-renewal of long term culture initiating cell by inhibiting TGFbR2 expression. CD34+ HSCs were isolated from cord blood units with MACS column. SiRNA against TGFbR2 was transfected by Lipofectamine [TM] RNAiMAX as transfection reagent. HSCs were cultured in IMDM medium containing 10% FBS and early acting cytokines [Flt3L, SCF, Tpo] for 8 days. Then we evaluated TGFbR2 expression by QRT-PCR. The CD34+ subpopulation of cultured cells were examined by flow cytometry on the 8th day. Finally the expanded cells were evaluated for the presence of early hematopoietic stem cells by LT-CIC and clonogenic assays. According to our results, TGFbR2 down regulation increases CD34+ subpopulation of HSCs. In addition, LT-CIC assay showed an enhancement in primitive hematopoietic stem cell capable of self-renewal. All in all, it seems that positive regulators have attracted more attention in the field of HSCs expansion while negative regulators have same importance in self-renewal process of HSCs and their inhibition can be a beneficial tool for enhancement of HSCs self-renewa