Proportion of CD34+CD38−CD123+ Leukemia Stem Cells at Diagnosis Varies in ELN Risk Groups and an Emerging Novel Marker for Prognosticating the Intermediate Risk patients of Acute Myeloid Leukemia: A Prospective Study

Mishra, Pravas; Tyagi, Seema; Sharma, Rahul Kumar; Halder, Rohan; Pati, Hara Prasad; Saxena, Renu; Mahapatra, Manoranjan

doi:10.1007/s12288-020-01383-9

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“… 18 - 21 Contributing to its attractiveness as a target in AML are studies reporting a correlation between higher CD123-positive leukemic stem/progenitor cell burden and worse outcome with AML chemotherapy. 26 , 27 Subsets of AML perhaps particularly suitable for CD123-targeted therapies are NPM1-mutated leukemias 28 and cases featuring an expansion of plasmacytoid dendritic cells (pDCs), cells that are readily identified based on high expression of CD123. 29 , 30 pDC-AML is a recently recognized disease entity encompassing approximately 5% of AML cases that is characterized by a high frequency of RUNX1 mutations.…”

Section: Discussionmentioning

confidence: 99%

Development of [211At]astatine-based anti-CD123 radioimmunotherapy for acute leukemias and other CD123+ malignancies

et al. 2022

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Radioimmunotherapy (RIT) has long been pursued to improve outcomes in acute leukemia and higher-risk myelodysplastic syndrome. Of increasing interest are alpha particle-emitting radionuclides such as astatine-211 ( 211 At) as they deliver large amounts of radiation over just a few cell diameters, enabling efficient and selective target cell kill. Here, we developed 211 At-based RIT targeting CD123, an antigen widely displayed on acute leukemia and MDS cells including underlying neoplastic stem cells. We generated and characterized new murine monoclonal antibodies (mAbs) specific for human CD123 and selected four, all of which were internalized by CD123+ target cells, for further characterization. All mAbs could be conjugated to a boron cage, isothiocyanatophenethyl-ureido- closo -decaborate(2-) (B10), and labeled with 211 At. CD123+ cell targeting studies in immunodeficient mice demonstrated specific uptake of 211 At-labeled anti-CD123 mAbs in human CD123+ MOLM-13 cell tumors in the flank. In mice injected intravenously with MOLM-13 cells or a CD123 NULL MOLM-13 subline, a single dose of up to 40 μCi of 211 At delivered via anti-CD123 mAb decreased tumor burdens and significantly prolonged survival dose-dependently in mice bearing CD123+ but not CD123− leukemia xenografts, demonstrating potent and target-specific in vivo anti-leukemia efficacy. These data support the further development of 211 At-CD123 RIT toward clinical application.

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