Prognostic Value of Transferrin Receptor-1 (CD71) Expression in Acute Lymphoblastic Leukemia

Hagag, Adel A; Badraia, Ibrahim M; Abdelmageed, Mohamed; Hablas, Nahed Mohammed; Hazzaa, Sahar M.; Nosair, Nahla A

doi:10.2174/1871530318666180605094706

Cited by 18 publications

(10 citation statements)

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“…In fact, TfR1 has been identified as a universal cancer marker (55). Increased expression of TfR1 correlates with advanced stage and/or poorer prognosis in a number of cancers, including solid cancers such as esophageal squamous cell carcinoma (56), breast cancer (57, 58), ovarian cancer (59), lung cancer (60), cervical cancer (61), bladder cancer (62), osteosarcoma (63), pancreatic cancers (64), cholangiocarcinoma (65), renal cell carcinoma (66), hepatocellular carcinoma (67,68), adrenal cortical carcinoma (69), and cancers of the nervous system (70) as well as hematopoietic malignancies such as acute lymphoblastic leukemia (ALL) (71,72), chronic lymphocytic leukemia (CLL) (73), and non-Hodgkin lymphoma (NHL) (73,74). Interestingly, patients infected with the human immunodeficiency virus (HIV) often develop more aggressive NHL that have been shown to express even higher levels of TfR1 messenger RNA compared to NHL cells from non-infected patients (75,76).…”

Section: Tfr1 Expression In Normal and Cancer Cellsmentioning

confidence: 99%

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

et al. 2021

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The transferrin receptor 1 (TfR1), also known as cluster of differentiation 71 (CD71), is a type II transmembrane glycoprotein that binds transferrin (Tf) and performs a critical role in cellular iron uptake through the interaction with iron-bound Tf. Iron is required for multiple cellular processes and is essential for DNA synthesis and, thus, cellular proliferation. Due to its central role in cancer cell pathology, malignant cells often overexpress TfR1 and this increased expression can be associated with poor prognosis in different types of cancer. The elevated levels of TfR1 expression on malignant cells, together with its extracellular accessibility, ability to internalize, and central role in cancer cell pathology make this receptor an attractive target for antibody-mediated therapy. The TfR1 can be targeted by antibodies for cancer therapy in two distinct ways: (1) indirectly through the use of antibodies conjugated to anti-cancer agents that are internalized by receptor-mediated endocytosis or (2) directly through the use of antibodies that disrupt the function of the receptor and/or induce Fc effector functions, such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Although TfR1 has been used extensively as a target for antibody-mediated cancer therapy over the years, interest continues to increase for both targeting the receptor for delivery purposes and for its use as direct anti-cancer agents. This review focuses on the developments in the use of antibodies targeting TfR1 as direct anti-tumor agents.

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Section: Tfr1 Expression In Normal and Cancer Cellsmentioning

confidence: 99%

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

et al. 2021

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“…The systematic iron pool in patients with leukemia is also increased, which is aggravated by multiple red-blood-cell transfusions. Multiple experimental and epidemiological studies have demonstrated the relationship between dysregulation of iron metabolism with the occurrence and progress of leukemia [9–11].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, poorly differentiated primary AML blasts tend to express higher levels of TfR1 than partially differentiated AML blasts [52]. TfR1 expression is higher in patients with T-cell ALL than patients with B-cell ALL [11, 54]. Clinical analysis also shows that overexpression of TfR1 in ALL is an adverse prognostic factor [11].…”

Section: Introductionmentioning

confidence: 99%

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Iron and leukemia: new insights for future treatments

Wang

Zhao

et al. 2019

J Exp Clin Cancer Res

123

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Iron, an indispensable element for life, is involved in all kinds of important physiological activities. Iron promotes cell growth and proliferation, but it also causes oxidative stress damage. The body has a strict regulation mechanism of iron metabolism due to its potential toxicity. As a cancer of the bone marrow and blood cells, leukemia threatens human health seriously. Current studies suggest that dysregulation of iron metabolism and subsequent accumulation of excess iron are closely associated with the occurrence and progress of leukemia. Specifically, excess iron promotes the development of leukemia due to the pro-oxidative nature of iron and its damaging effects on DNA. On the other hand, leukemia cells acquire large amounts of iron to maintain rapid growth and proliferation. Therefore, targeting iron metabolism may provide new insights for approaches to the treatment of leukemia. This review summarizes physiologic iron metabolism, alternations of iron metabolism in leukemia and therapeutic opportunities of targeting the altered iron metabolism in leukemia, with a focus on acute leukemia.

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“…Generally, the current tumor staging systems fails to adequately predict the prognosis of numerous cancers, underlying the need for urgent identification of biomarkers for accurate tumor diagnosis and prognosis. Growing evidence shows that aberrant iron metabolism participates in AML initiation, progression, and infiltration of immune cells to the microenvironment (Kennedy et al, 2014;Benadiba et al, 2017;Hagag et al, 2018). Numerous studies have implicated dysregulated expression of IMRGs in cancer progression (Li et al, 2020;Zhu et al, 2021;Song et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

LIU¹,

HUANG²

2023

Biocell

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Iron metabolism maintains the balance between iron absorption and excretion. Abnormal iron metabolism can cause numerous diseases, including tumor. This study determined the iron metabolism-related genes (IMRGs) signature that can predict the prognosis of acute myeloid leukemia (AML). The roles of these genes in the immune microenvironment were also explored. Methods: A total of 514 IMRGs were downloaded from the Molecular Characteristics Database (MSigDB). IMRGs related to AML prognosis were identified using Cox regression and LASSO analyses and were used to construct the risk score model. AML patients were stratified into high-risk groups (cluster 1) and low-risk groups (cluster 2) based on the mean value of the risk score. The accuracy and prognosis prediction potential of the risk-score model was evaluated using Kaplan-Meier and receiver operating characteristics analysis. The stromal score, immune scores, and immune cells infiltrated in AML samples were estimated using CIBERSORT, MCPcountre, and Xcell algorithms. The role of immune checkpoint genes in the AML microenvironment and the prognostic value of the IMRGs were also evaluated. Results: An AML prognosis prediction model was established based on the eight most critical IMRGs. Further analyses revealed that the model could accurately predict AML prognosis. The expression of IMRGs correlated with the infiltration of several immune cells and could influence response to certain chemotherapy drugs and immunotherapy. Conclusion: A model based on IMRGs can accurately predict the overall survival and disease-free survival of AML patients.

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Prognostic Value of Transferrin Receptor-1 (CD71) Expression in Acute Lymphoblastic Leukemia

Abstract: 'Positive Transferrin receptor -1 (CD71) expression in patients with ALL is adverse prognostic factor and should be taken in consideration in designing future therapeutic strategies based on patient- specific risk factors'.

Cited by 18 publications

References 0 publications

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents

Iron and leukemia: new insights for future treatments

A model based on eight iron metabolism-related genes accurately predicts acute myeloid leukemia prognosis

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