Shady Adnan Awad, Olli Dufva, Jay Klievink, Ella Karjalainen, Aleksandr Ianevski, Paavo Pietarinen, Daehong Kim, Swapnil Potdar, Maija Wolf, Kourosh Lotfi, Tero Aittokallio, Krister Wennerberg, Kimmo Porkka, Satu Mustjoki
BCR::ABL1-independent pathways contribute to primary resistance to tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) and play a role in leukemic stem cell persistence. Here, we perform ex vivo drug screening of CML CD34+ leukemic stem/progenitor cells using 100 single drugs and TKI-drug combinations and identify sensitivities to Wee1, MDM2, and BCL2 inhibitors. These agents effectively inhibit primitive CD34+ CD38- CML cells and demonstrate potent synergies when combined with TKIs...
April 10, 2024: Cell reports medicine