scholarly journals Wnt/ß-Catenin: A New Therapeutic Approach to Acute Myeloid Leukemia

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Y. Kim ◽  
S. Thanendrarajan ◽  
I. G. H. Schmidt-Wolf
Keyword(s):  
Acute Myeloid Leukemia ◽  
Wnt Signaling ◽  
Therapeutic Approach ◽  
Myeloid Leukemia ◽  
Wnt Pathway ◽  
Treatment Strategies ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Acute Myeloid

Recent studies have shown genetic and epigenetic aberrations resulting in aberrant activation of the Wingless-Int (Wnt) pathway, thus influencing the initiation and progression of acute myeloid leukemia (AML). Of major importance, these findings may lead to novel treatment strategies exploiting targeted modulation of Wnt signaling. This paper comprises the latest status of knowledge concerning the role of Wnt pathway alteration in AML and outlines future lines of research and their clinical perspectives.

scholarly journals The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia

Leukemia ◽  
2007 ◽  
Vol 21 (8) ◽  
pp. 1638-1647 ◽  
Author(s):  
J-H Mikesch ◽  
B Steffen ◽  
W E Berdel ◽  
H Serve ◽  
C Müller-Tidow
Keyword(s):  
Acute Myeloid Leukemia ◽  
Wnt Signaling ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Angiogenesis in Acute Myeloid Leukemia and Opportunities for Novel Therapies

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Angelica Trujillo ◽  
Christie McGee ◽  
Christopher R. Cogle
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Treatment Strategies ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Autocrine Stimulation ◽  
Novel Treatment Strategies ◽  
Relapsed Disease ◽  
Acute Myeloid

Acute myeloid leukemia (AML) arises from neoplastic transformation of hematopoietic stem and progenitor cells, and relapsed disease remains one of the greater challenges in treating this hematologic malignancy. This paper focuses on angiogenic aspects of AML including the significance and prognostic value of bone marrow microvessel density and circulating cytokine levels. We show three general mechanisms whereby AML exploits angiogenic pathways, including direct induction of angiogenesis, paracrine regulation, and autocrine stimulation. We also present early evidence that leukemia cells contribute directly to vascular endothelia. Novel treatment strategies are proposed, and a review of relevant antiangiogenic clinical trials is presented. By understanding how blood vessels can serve as a reservoir for refractory and relapsed AML, new diagnostics and promising treatment strategies can be developed.

scholarly journals Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications

2021 ◽  
Vol 5 (16) ◽  
pp. 3102-3112
Author(s):  
Marta Lopes ◽  
Tiago L. Duarte ◽  
Maria J. Teles ◽  
Laura Mosteo ◽  
Sérgio Chacim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mouse Model ◽  
Myeloid Leukemia ◽  
Transferrin Saturation ◽  
Treatment Strategies ◽  
Leukemic Cells ◽  
Cancer Types ◽  
Iron Profile ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer, but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in patients with AML at diagnosis and explored the mechanisms involved using the syngeneic MLL-AF9–induced AML mouse model. We found that AML is a disorder with a unique iron profile, not associated with inflammation or transfusion, characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that the AML-induced loss of erythroblasts is responsible for iron redistribution and increased TSAT. We also show that AML progression is delayed in mouse models of systemic iron overload and that elevated TSAT at diagnosis is independently associated with increased overall survival in AML. We suggest that TSAT may be a relevant prognostic marker in AML.

scholarly journals Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications

2020 ◽  
Author(s):  
Marta Lopes ◽  
Tiago L. Duarte ◽  
Maria J. Teles ◽  
Laura Mosteo ◽  
Sérgio Chacim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mouse Model ◽  
Myeloid Leukemia ◽  
Transferrin Saturation ◽  
Treatment Strategies ◽  
Leukemic Cells ◽  
Cancer Types ◽  
Iron Profile ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in AML patients at diagnosis and mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile not associated with inflammation or transfusion and characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that leukemic blasts take up iron and that the AML-induced loss of erythroblasts is responsible for iron redistribution and an increase in TSAT. We also show that elevated TSAT at diagnosis is independently associated with increased overall survival in AML and suggest that TSAT may be a relevant prognostic marker in AML.

Recurrent and reversible bilateral palmar blue discoloration following administration of liposomal daunorubicin-cytarabine (Vyxeos®) for acute myeloid leukemia with myelodysplasia-related changes

2020 ◽  
pp. 107815522097845
Author(s):  
Katherine Triesel ◽  
Timothy Chiang ◽  
Robert Seabury ◽  
Christopher Miller
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Liposomal Daunorubicin ◽  
Therapeutic Modalities ◽  
First Case ◽  
Blue Discoloration ◽  
Novel Treatment Strategies ◽  
Acute Myeloid

Introduction With novel treatment strategies for acute myeloid leukemia becoming more readily utilized in the clinical practice setting, new data on potential treatment-related adverse events also has become available. Case report We present a patient case on a previously unreported potential adverse event related to liposomal daunorubicin-cytarabine administration. The patient experienced bilateral discoloration of the palms of his hands that resolved after completion of the treatment cycle, only to recur at cycle two of therapy. Management and outcome: No intervention was required as the condition resolved within a week of onset. Discussion With newer therapeutic modalities becoming more used in the clinical setting, it is important to understand the potential risks of treatment-related adverse events that come with them. To our knowledge this is the first case reporting blue-skin discoloration related to liposomal daunorubicin-cytarabine.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

scholarly journals Leukemia stem cell-bone marrow microenvironment interplay in acute myeloid leukemia development

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yiyi Yao ◽  
Fenglin Li ◽  
Jiansong Huang ◽  
Jie Jin ◽  
Huafeng Wang
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chemotherapy Resistance ◽  
Bone Marrow Microenvironment ◽  
Cytotoxic Effects ◽  
High Relapse Rate ◽  
Underlying Mechanisms ◽  
Acute Myeloid

AbstractDespite the advances in intensive chemotherapy regimens and targeted therapies, overall survival (OS) of acute myeloid leukemia (AML) remains unfavorable due to inevitable chemotherapy resistance and high relapse rate, which mainly caused by the persistence existence of leukemia stem cells (LSCs). Bone marrow microenvironment (BMM), the home of hematopoiesis, has been considered to play a crucial role in both hematopoiesis and leukemogenesis. When interrupted by the AML cells, a malignant BMM formed and thus provided a refuge for LSCs and protecting them from the cytotoxic effects of chemotherapy. In this review, we summarized the alterations in the bidirectional interplay between hematopoietic cells and BMM in the normal/AML hematopoietic environment, and pointed out the key role of these alterations in pathogenesis and chemotherapy resistance of AML. Finally, we focused on the current potential BMM-targeted strategies together with future prospects and challenges. Accordingly, while further research is necessary to elucidate the underlying mechanisms behind LSC–BMM interaction, targeting the interaction is perceived as a potential therapeutic strategy to eradicate LSCs and ultimately improve the outcome of AML.

Sign in / Sign up

Export Citation Format

Share Document