506 POSTER The apogenic anti-CD9 antibody, AR40A746.2.3, inhibits tumor growth in breast and pancreatic cancer and targets cancer stem cells in acute myeloid leukemia

2008 ◽  
Vol 6 (12) ◽  
pp. 161
Author(s):  
J. Menendez ◽  
L. Jin ◽  
A.G. Poeppl ◽  
K. O'Reilly ◽  
R.H. Brunet ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Discovery of proangiogenic CD44+mesenchymal cancer stem cells in an acute myeloid leukemia patient’s bone marrow

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Huynh Cao ◽  
Jeffrey Xiao ◽  
Mark E. Reeves ◽  
Kimberly Payne ◽  
Chien Shing Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cancer Stem Cells ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia

2019 ◽  
Vol 25 (1) ◽  
pp. 137-148.e6 ◽  
Author(s):  
Jasmin Paris ◽  
Marcos Morgan ◽  
Joana Campos ◽  
Gary J. Spencer ◽  
Alena Shmakova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Cancer Stem Cells ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy

2021 ◽  
Vol 70 (1) ◽  
pp. 83-97
Author(s):  
Remco J. Molenaar ◽  
Johanna W. Wilmink
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Cancer Stem Cells ◽  
Myeloid Leukemia ◽  
Clinical Effects ◽  
Differentiation Therapy ◽  
Isocitrate Dehydrogenase 1 ◽  
Cells Of Origin ◽  
Mutant Idh1 ◽  
Acute Myeloid

Isocitrate dehydrogenase 1 and 2 (IDH1/2) are enzymes recurrently mutated in various types of cancer, including glioma, cholangiocarcinoma, chondrosarcoma, and acute myeloid leukemia. Mutant IDH1/2 induce a block in differentiation and thereby contribute to the stemness and oncogenesis of their cells of origin. Recently, small-molecule inhibitors of mutant IDH1/2 have been Food and Drug Administration–approved for the treatment of IDH1/2-mutated acute myeloid leukemia. These inhibitors decrease the stemness of the targeted IDH1/2-mutated cancer cells and induce their differentiation to more mature cells. In this review, we elucidate the mechanisms by which mutant IDH1/2 induce a block in differentiation and the biological and clinical effects of the release into differentiation by mutant-IDH1/2 inhibitors. (J Histochem Cytochem 70:83–97, 2022)

scholarly journals Nuclear NAD+ homeostasis governed by NMNAT1 prevents apoptosis of acute myeloid leukemia stem cells

2021 ◽  
Vol 7 (30) ◽  
pp. eabf3895
Author(s):  
Xiangguo Shi ◽  
Yajian Jiang ◽  
Ayumi Kitano ◽  
Tianyuan Hu ◽  
Rebecca L. Murdaugh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Cancer Stem Cells ◽  
Myeloid Leukemia ◽  
Leukemia Stem Cells ◽  
Hematopoietic Stem ◽  
Metabolic Dysregulation ◽  
Proliferation And Differentiation ◽  
Xenograft Models ◽  
Acute Myeloid

Metabolic dysregulation underlies malignant phenotypes attributed to cancer stem cells, such as unlimited proliferation and differentiation blockade. Here, we demonstrate that NAD+ metabolism enables acute myeloid leukemia (AML) to evade apoptosis, another hallmark of cancer stem cells. We integrated whole-genome CRISPR screening and pan-cancer genetic dependency mapping to identify NAMPT and NMNAT1 as AML dependencies governing NAD+ biosynthesis. While both NAMPT and NMNAT1 were required for AML, the presence of NAD+ precursors bypassed the dependence of AML on NAMPT but not NMNAT1, pointing to NMNAT1 as a gatekeeper of NAD+ biosynthesis. Deletion of NMNAT1 reduced nuclear NAD+, activated p53, and increased venetoclax sensitivity. Conversely, increased NAD+ biosynthesis promoted venetoclax resistance. Unlike leukemia stem cells (LSCs) in both murine and human AML xenograft models, NMNAT1 was dispensable for hematopoietic stem cells and hematopoiesis. Our findings identify NMNAT1 as a previously unidentified therapeutic target that maintains NAD+ for AML progression and chemoresistance.

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