MSGID: 1:317/3 63f83d73   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New promising targeted drug for a rare leukemia    
      
     Date:   
         February 23, 2023   
     Source:   
         University of Helsinki   
     Summary:   
         Researchers have identified a possible new targeted drug for   
         treating acute myeloid leukemia. In the future, the discovery may   
         help patients with certain rare subtypes of the disease.   
      
      
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   FULL STORY   
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   Targeted drugs have been developed to supplement chemotherapy in the   
   treatment of cancer. These drugs only affect cancer cells, leaving   
   healthy cells alone.   
      
   Venetoclax is a new targeted therapy option for the treatment of acute   
   myeloid leukemia (AML). Venetoclax was recently granted marketing   
   authorisation in Finland.   
      
      
   ==========================================================================   
   Venetoclax works by sensitising cancer cells to programmed cell   
   death. However, a new study now shows that venetoclax does not appear to   
   be effective against erythroid and megakaryoblastic leukemias, two rare   
   subtypes of the disease that are difficult to treat. In these leukemia   
   types, malignant cells resemble blood stem cells that produce red blood   
   cells or platelets. Currently, few treatment options are available to   
   these patients.   
      
   The study carried out by the University of Helsinki, HUS Comprehensive   
   Cancer Center and the University of Copenhagen identified a new targeted   
   drug, which may in the future offer a therapeutic option to patients   
   with these subtypes of the disease.The study was published in the Blood   
   journal in December.   
      
   Further research needed In the laboratory, the researchers screened a wide   
   selection of pharmaceutical agents that could be effective specifically   
   against erythroid or megakaryoblastic leukemia cells.   
      
   Among the more than 500 agents analysed, BCL-XL protein inhibitors   
   in particular were effective in killing cancer cells isolated from   
   these types of leukemia. The BCL-XL protein has a similar function of   
   preventing cells from being driven to programmed cell death as BCL-2,   
   the target of venetoclax. At the moment, BCL-XL inhibitors are not used   
   to treat patients, but their efficacy and safety are currently being   
   investigated in clinical trials.   
      
   "The introduction of venetoclax has significantly improved the prognosis   
   of AML patients. However, our research indicates that venetoclax is   
   unlikely to function optimally against the subtypes of AML in our   
   focus. Nevertheless, the finding should be verified in larger patient   
   datasets," says physician- scientist Olli Dufva.   
      
   Potential to improve prognosis AML is the most common type of acute   
   leukemia in adults. It can be divided into subtypes based on mutations and   
   the degree of differentiation of leukemia cells. One challenge associated   
   with the use of targeted drugs is identifying patients who benefit from   
   the new drug options. This study contributes to making the selection of   
   targeted drugs more precise.   
      
   "The laboratory findings provide evidence that patients with erythroid   
   or megakaryoblastic acute leukemia would be a promising group for   
   investigating the efficacy of BCL-XL inhibitors in clinical use," says   
   postdoctoral researcher Heikki Kuusanma"ki.   
      
   The researchers believe that BCL-XL inhibitors will be trialled in the   
   treatment of these leukemia types in the near future.   
      
   "This finding may in the future improve the prognosis of these very   
   rare and difficult-to-treat leukemias," says Professor of Translational   
   Haematology Satu Mustjoki from the University of Helsinki and HUS   
   Comprehensive Cancer Center.   
      
   The study was funded by the Academy of Finland, Cancer Foundation Finland,   
   the Finnish Cancer Institute, Sigrid Juse'lius Foundation and the Finnish   
   Medical Foundation. The study was carried out under the iCAN Digital   
   Precision Cancer Medicine Flagship funded by the Academy of Finland.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Leukemia # Lung_Cancer # Cancer # Brain_Tumor #   
                   Prostate_Cancer # Personalized_Medicine # Lymphoma #   
                   Skin_Cancer   
       * RELATED_TERMS   
             o Drug_discovery o Delirium o Stem_cell_treatments o   
             Pharmaceutical_company o Narcotic o Functional_training o   
             Huntington's_disease o Esophageal_cancer   
      
   ==========================================================================   
   Story Source: Materials provided by University_of_Helsinki. Note:   
   Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Heikki Kuusanma"ki, Olli Dufva, Markus Va"ha"-Koskela, Aino-Maija   
      Leppa",   
         Jani Huuhtanen, Ida Maria Va"nttinen, Petra Johanna Nygren, Jay   
         Klievink, Jonas Otto Vilhelm Bouhlal, Petri Po"lo"nen, Qi Zhang,   
         Shady Adnan Awad, Cristina Mancebo-Pe'rez, Joseph Saad, Juho   
         J. Miettinen, Komal Kumar Javarappa, Sofia Aakko, Tanja Ruokoranta,   
         Samuli Eldfors, Merja Heina"niemi, Kim Theilgaard-Mo"nch, Ulla   
         Wartiovaara-Kautto, Mikko A I Kera"nen, Kimmo Porkka, Marina   
         Konopleva, Krister Wennerberg, Mika Kontro, Caroline A. Heckman,   
         Satu Mustjoki. Erythroid/megakaryocytic differentiation confers   
         BCL-XL dependency and venetoclax resistance in acute myeloid   
         leukemia. Blood, 2022; DOI: 10.1182/blood.2021011094   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/02/230223132919.htm   
      
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