scholarly journals Alterations in the deleted in colorectal carcinoma gene in human primary leukemia

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 927-930 ◽  
Author(s):  
K Miyake ◽  
K Inokuchi ◽  
K Dan ◽  
T Nomura
Keyword(s):  
Colorectal Carcinoma ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Pcr Analysis ◽  
Allelic Loss ◽  
Acute Myelogenous ◽  
Dcc Gene ◽  
Polymerase Chain ◽  
Deleted In Colorectal Carcinoma

To evaluate the role of the deleted in colorectal carcinoma (DCC) gene in leukemogenesis, we examined loss of heterozygosity (LOH) in the DCC gene in 64 primary human leukemias using Southern blot analysis and examined the expression of the DCC gene using reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Allelic loss in the DCC gene was observed in two patients (6%, 2 of 35 informative cases), and expression of the DCC gene was reduced or absent in 8 of 26 (31%) patients with acute myelogenous leukemia (AML), 3 of 9 (33%) patients with acute lymphocytic leukemia (ALL), and 7 of 29 (24%) patients with chronic myelogenous leukemia (CML). Moreover, in one ALL patient with absent DCC expression at diagnosis, its expression became normal after performing chemotherapy and achieving remission. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.

scholarly journals Alterations in the deleted in colorectal carcinoma gene in human primary leukemia

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 927-930 ◽  
Author(s):  
K Miyake ◽  
K Inokuchi ◽  
K Dan ◽  
T Nomura
Keyword(s):  
Colorectal Carcinoma ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Pcr Analysis ◽  
Allelic Loss ◽  
Acute Myelogenous ◽  
Dcc Gene ◽  
Polymerase Chain ◽  
Deleted In Colorectal Carcinoma

Abstract To evaluate the role of the deleted in colorectal carcinoma (DCC) gene in leukemogenesis, we examined loss of heterozygosity (LOH) in the DCC gene in 64 primary human leukemias using Southern blot analysis and examined the expression of the DCC gene using reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Allelic loss in the DCC gene was observed in two patients (6%, 2 of 35 informative cases), and expression of the DCC gene was reduced or absent in 8 of 26 (31%) patients with acute myelogenous leukemia (AML), 3 of 9 (33%) patients with acute lymphocytic leukemia (ALL), and 7 of 29 (24%) patients with chronic myelogenous leukemia (CML). Moreover, in one ALL patient with absent DCC expression at diagnosis, its expression became normal after performing chemotherapy and achieving remission. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.

The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1

1993 ◽  
Vol 13 (7) ◽  
pp. 4284-4290
Author(s):  
M A Brach ◽  
H J Gruss ◽  
C Sott ◽  
F Herrmann
Keyword(s):  
Tumor Necrosis ◽  
Growth Stimulation ◽  
Myelogenous Leukemia ◽  
Tnf Alpha ◽  
Mitogenic Response ◽  
Necrosis Factor Alpha ◽  
Acute Myelogenous ◽  
Factor Alpha ◽  
Necrosis Factor

In the present study, we addressed the role of the c-jun proto-oncogene in the mitogenic response of human fibroblasts and primary acute myelogenous leukemia blasts to tumor necrosis factor alpha (TNF-alpha). Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun, resulting in accumulation of c-jun mRNA and protein expression. In order to elucidate the role of c-Jun/AP-1 in TNF-mediated growth stimulation, the antisense (AS) technique was used. Uptake studies of oligonucleotides were performed with fibroblasts, demonstrating that incorporation of oligomers was maximal at 4 h. Oligodeoxynucleotides remained stable in these cells for up to 24 h. Treatment of fibroblasts with the AS oligonucleotide resulted in intracellular duplex formation followed by an efficient translation blockade of c-Jun/AP-1. In contrast, sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c-Jun/AP-1, suggesting specific elimination of c-Jun/AP-1 by the AS oligomer. Fibroblasts cultured in the presence of the AS oligonucleotide but not those cultured in the presence of the S or NS oligonucleotide failed to respond proliferatively to TNF-alpha. These findings could be confirmed by experiments with primary acute myelogenous leukemia blasts, which also demonstrated that TNF-induced growth stimulation required c-Jun/AP-1 function. Taken together, our results indicate that activation of c-Jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF, which leads to a proliferative response of its target cells.

scholarly journals Elevated Expression of the Apoptotic Regulator Mcl-1 at the Time of Leukemic Relapse

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 991-1000 ◽  
Author(s):  
Scott H. Kaufmann ◽  
Judith E. Karp ◽  
Phyllis A. Svingen ◽  
Stan Krajewski ◽  
Philip J. Burke ◽  
...  
Keyword(s):  
Initial Therapy ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Paired Samples ◽  
Elevated Expression ◽  
Leukemic Relapse ◽  
Acute Myelogenous ◽  
Weak Negative Correlation ◽  
Apoptosis Inhibitor

Abstract Bcl-2, Bcl-xL, and Mcl-1 are three related intracellular polypeptides that have been implicated as negative regulators of apoptosis. In contrast, the partner protein Bax acts as a positive regulator of apoptosis. Based on the observation that all four of these polypeptides are expressed in a variety of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) cell lines, cellular levels of these polypeptides were examined by immunoblotting in bone marrow samples harvested from 123 adult AML patients and 36 adult ALL patients before initial antileukemic therapy. Levels of Bcl-2, Mcl-1, Bcl-xL, and Bax each varied over a more than 10-fold range in different pretreatment leukemia specimens. When the 54 AML and 23 ALL samples that contained greater than 80% malignant cells were examined in greater detail, it was observed that pretreatment levels of Bcl-2 and Mcl-1 correlated with each other (R = .44,P < .001 for AML and R = .79,P < .0001 for ALL). In addition, a weak negative correlation between Bax expression and age was observed in AML samples (R = −0.35, P < .02) but not ALL samples. There was no relationship between pretreatment levels of these polypeptides and response to initial therapy. However, examination of 19 paired samples (the first harvested before chemotherapy and the second harvested 23 to 290 days later at the time of leukemic recurrence) revealed a greater than or equal to twofold increase in Mcl-1 levels in 10 of 19 pairs (7 of 15 AML and 3 of 4 ALL) at recurrence. In contrast, 2 of 19 pairs contained twofold less Mcl-1 at the time of recurrence. Approximately equal numbers of samples showed twofold increases and decreases in Bcl-2 (5 increases, 3 decreases) and Bcl-xL (1 increase, 4 decreases) at recurrence. Bax levels did not show a twofold decrease in any patient. These results, coupled with recent observations that cells overexpressing Mcl-1 are resistant to a variety of chemotherapeutic agents, raise the possibility that some chemotherapeutic regimens might select for leukemia cells with elevated levels of this particular apoptosis inhibitor.

scholarly journals MicroRNAs as Haematopoiesis Regulators

2013 ◽  
Vol 2013 ◽  
pp. 1-20 ◽  
Author(s):  
Ram Babu Undi ◽  
Ravinder Kandi ◽  
Ravi Kumar Gutti
Keyword(s):  
Blood Cells ◽  
Erythroid Differentiation ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
Complex Process ◽  
Development And Differentiation ◽  
Multiple Myelomas

The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis.

Diagnostic value of serum miR-145 and miR-185 as targeting of the APRIL oncogene in the B-cell chronic lymphocytic leukemia

2020 ◽  
Author(s):  
Malihe Bagheri ◽  
Behzad Khansarinejad ◽  
Ghasem Mosayebi ◽  
Alireza Moradabadi ◽  
Mahdieh Mondanizadeh
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hematologic Malignancy ◽  
Rna Extraction ◽  
Diagnostic Value ◽  
Lymphocytic Leukemia ◽  
Pcr Analysis ◽  
Healthy Individuals ◽  
Potential Biomarker ◽  
New Biomarkers

Abstract Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematologic malignancy in adults worldwide. This cancer has a poor prognosis at different stages. So, the identification of new biomarkers is important for early diagnosis of B-CLL. Considering the oncogenic role of APRIL molecule in this leukemia as well as the regulatory role of microRNAs (miRNAs) in different signaling pathways, the present study evaluated the miRNAs targeting APRIL gene in B-CLL.Methods: The miRNAs were predicted and selected using bioinformatics algorithms. A total of 80 plasma samples (40 samples of healthy individuals and 40 samples of B-CLL patients) were subjected to RNA extraction and synthesis of cDNA. The expressions levels of predicted miRNAs and APRIL gene in plasma of B-CLL patients and healthy individuals were assessed by Real time PCR analysis. ROC analysis was performed to investigate the role predicted miRNAs as novel biomarkers in diagnosis of B-CLL. Results: The results of the prediction showed that miR-145-5p and miR-185-5p target the APRIL gene. The expression level of APRIL gene was strikingly higher in plasma of B-CLL patients than in the healthy individuals (102, P= 0.001). On the other hand, expression levels of miR-145-5p and miR-185-5p were strikingly lower in B-CLL patients than in the healthy individuals (0.07, P= 0.001) (0.29, P= 0.001). Also, ROC curve analyses demonstrated that miR-145-5p and miR-185-5p are specific and sensitive and may serve as new biomarkers for the early detection of B-CLL. Conclusions: These data suggest that the study miRNAs may have a role in B-CLL development and progression. Moreover, miR-145-5p and miR-185-5p can be served as a novel and potential biomarker in the diagnosis of B-CLL.

scholarly journals Mechanistic insight into WEB-2170-induced apoptosis in human acute myelogenous leukemia cells: The crucial role of PTEN

2009 ◽  
Vol 37 (10) ◽  
pp. 1176-1185.e21 ◽  
Author(s):  
Cristina Cellai ◽  
Anna Laurenzana ◽  
Elisa Bianchi ◽  
Sara Sdelci ◽  
Rossella Manfredini ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Crucial Role ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Mechanistic Insight ◽  
Acute Myelogenous ◽  
Induced Apoptosis ◽  
Insight Into

scholarly journals Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4789-4796 ◽  
Author(s):  
T Miyamoto ◽  
K Nagafuji ◽  
K Akashi ◽  
M Harada ◽  
T Kyo ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Acute Myelogenous Leukemia ◽  
Fusion Gene ◽  
Phosphoglycerate Kinase ◽  
Myelogenous Leukemia ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Differentiation Potential ◽  
Acute Myelogenous

The leukemia-specific AML1/ETO fusion gene has been shown to be detected by reverse transcriptase polymerase chain reaction (RT-PCR) analysis in patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. In the present study, the AML1/ETO mRNA could be detected by RT-PCR in bone marrow (BM) and/or peripheral blood (PB) samples from all 18 patients who had been maintaining complete remission for 12 to 150 months (median, 45 months) following chemotherapy or PB stem cell transplantation (PBSCT), whereas it could not be detected in four patients who had been maintaining remission for more than 30 months following allogeneic BM transplantation (BMT). We surveyed the expression of AML1/ETO mRNA in clonogenic progenitors from BM in these cases. Notably, 51 of 2,469 colonies from clonogenic progenitors (2.1%) expressed the AML1/ETO mRNA in 18 cases who were RT- PCR+ in BM and/or PB samples. Expression was observed in various clonogenic progenitors, including granulocyte-macrophage colonies, mixed colonies, erythroid colonies, and megakaryocyte colonies. Furthermore, we analyzed the clonality of these progenitors by X- chromosome inactivation patterns of the phosphoglycerate kinase (PGK) gene in four female patients. The AML1/ETO mRNA+ progenitors showed the PGK allele identical to that detected in the leukemic blasts from the time of initial diagnosis. Normal constitutive hematopoiesis was sustained by polyclonal BM reconstitution in these patients. Accordingly, these committed progenitor cells that express AML1/ETO mRNA during remission likely have arisen from common t(8;21)+ pluripotent progenitor cells with at least trilineage differentiation potential. These data strongly suggest that the origin of the clonogenic leukemic progenitors of t(8;21) AML may be multipotent hematopoietic progenitors that acquired the t(8;21) chromosomal abnormality.

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