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Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the peripheral blood. Nearly half of the AML patients relapse after standard induction therapy, and new forms of therapy are urgently needed. Chimeric antigen receptor (CAR) T therapy has so far not been successful in AML due to lack of efficacy and safety. Indeed, the most attractive antigen targets are stem cell markers such as CD33 or CD123. We demonstrate that CD37, a mature B cell marker, is expressed in AML samples, and its presence correlates with the European LeukemiaNet (ELN) 2017 risk stratification. We repurpose the anti-lymphoma CD37CAR for the treatment of AML and show that CD37CAR T cells specifically kill AML cells, secrete proinflammatory cytokines, and control cancer progression in vivo. Importantly, CD37CAR T cells display no toxicity toward hematopoietic stem cells. Thus, CD37 is a promising and safe CAR T cell AML target., Competing Interests: Declaration of interests The CD37CAR construct has been patented (WO2017118745A1) and E.M.I., G.K., and S.W. are listed among the inventors. S.K. has received honoraria from TCR2 Inc., Miltenyi, Novartis, BMS, and GSK. S.K. is inventor of several patents in the field of immuno-oncology. S.K. received license fees from TCR2 Inc. and Carina Biotech. S.K. received research support from TCR2 Inc., Plectonic GmBH, Tabby Therapeutics, and Arcus Bioscience for work unrelated to this manuscript. The funding agencies had no role in the conduction and management of the presented research and were not involved in the preparation of this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Shoot branching from axillary buds (AXBs) is regulated by a network of inhibitory and promotive forces, which includes hormones. In perennials, the dwarfed stature of the embryonic shoot inside AXBs is indicative of gibberellin (GA) deficiency, suggesting that AXB activation and outgrowth require GA. Nonetheless, the role of GA in branching has remained obscure. We here carried out comprehensive GA transcript and metabolite analyses in hybrid aspen, a perennial branching model. The results indicate that GA has an inhibitory as well as promotive role in branching. The latter is executed in two phases. While the expression level of GA2ox is high in quiescent AXBs, decapitation rapidly downregulated it, implying increased GA signaling. In the second phase, GA3ox2 -mediated de novo GA-biosynthesis is initiated between 12 and 24 h, prior to AXB elongation. Metabolite analyzes showed that GA 1/4 levels were typically high in proliferating apices and low in the developmentally inactive, quiescent AXBs, whereas the reverse was true for GA 3/6 . To investigate if AXBs are differently affected by GA 3 , GA 4 , and GR24, an analog of the branch-inhibitor hormone strigolactone, they were fed into AXBs of single-node cuttings. GA 3 and GA 4 had similar effects on GA and SL pathway genes, but crucially GA 3 induced AXB abscission whereas GA 4 promoted outgrowth. Both GA 3 and GA 4 strongly upregulated GA2ox g enes, which deactivate GA 1/4 but not GA 3/6 . Thus, the observed production of GA 3/6 in quiescent AXBs targets GA 1/4 for GA2ox-mediated deactivation. AXB quiescence can therefore be maintained by GA 3/6 , in combination with strigolactone. Our discovery of the distinct tasks of GA 3 and GA 4 in AXB activation might explain why the role of GA in branching has been difficult to decipher. Together, the results support a novel paradigm in which GA 3/6 maintains high levels of GA2ox expression and low levels of GA 4 in quiescent AXBs, whereas activation and outgrowth require increased GA 1/4 signaling through the rapid reduction of GA deactivation and subsequent GA biosynthesis., (Copyright © 2020 Katyayini, Rinne, Tarkowská, Strnad and van der Schoot.)

The biosynthesis and roles of strigolactones (SLs) have been investigated in herbaceous plants, but so far, their role in trees has received little attention. In this study, we analyzed the presence, spatial/temporal expression and role of SL pathway genes in Populus tremula � Populus tremuloides. In this proleptic species, axillary buds (AXBs) become para-dormant at the bud maturation point, providing an unambiguous starting point to study AXB activation. We identified previously undescribed Populus homologs of DWARF27 (D27), LATERAL BRANCHING OXIDOREDUCTASE (LBO) and DWARF53-like (D53-like) and analyzed the relative expression of all SL pathway genes in root tips and shoot tissues. We found that, although AXBs expressed MORE AXILLARY GROWTH1 (MAX1) and LBO, they did not express MAX3 and MAX4, whereas nodal bark expressed high levels of all SL biosynthesis genes. By contrast, expression of the SL perception and signaling genes MAX2, D14 and D53 was high in AXBs relative to nodal bark and roots. This suggests that AXBs are reliant on the associated nodes for the import of SLs and SL precursors. Activation of AXBs was initiated by decapitation and single-node isolation. This rapidly downregulated SL pathway genes downstream of MAX4, although later these genes were upregulated coincidently with primordia formation. GR24-feeding counteracted all activation-related changes in SL gene expression but did not prevent AXB outgrowth showing that SL is ineffective once AXBs are activated. The results indicate that nodes rather than roots supply SLs and its precursors to AXBs, and that SLs may restrain embryonic shoot elongation during AXB formation and para-dormancy in intact plants., (� The Author(s) 2019. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)