azacitidine

The DNA hypomethylating agents (HMAs) 5-azacitidine and decitabine are the backbone of disease modifying therapy in myelodysplastic syndromes (MDS). We show that pyrimethamine, an FDA-approved antifolate, induces apoptosis across leukemic models, synergizes with venetoclax, and restores sensitivity in HMA- and venetoclax-resistant leukemia. Pyrimethamine promotes differentiation of stem and progenitor cells in primary MDS samples and in combination with venetoclax directly inhibits pyrimidine synthesis, revealing a clinically actionable strategy to overcome a key mechanism of therapeutic resistance.

P=N/A, N=80, Not yet recruiting, Mianyang Central Hospital; Mianyang Central Hospital

P=N/A, N=111, Completed, The first affiliated hospital, Zhejiang University School of Medicine; The first affiliated hospital, Zhejiang University School of Medicine

P=N/A, N=34, Not yet recruiting, The Second Affiliated Hospital of Guangxi Medical University; The Second Affiliated Hospital of Guangxi Medical University

P=N/A, N=40, Not yet recruiting, the First Affiliated Hospital, Zhejiang University School of Medicine; The People's Hospital Affiliated to Ningbo University

P=N/A, N=20, Not yet recruiting, The First Affiliated Hospital of Xinjiang Medical University; The First Affiliated Hospital of Xinjiang Medical University

P=N/A, N=304, Recruiting, The Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; The Ninth People's Hospital Affiliated to Shanghai Jiao To

P2, N=26, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=142, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=17, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=216, Recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

On the other hand, the expression of BCL-XL and MCL1 in leukemia cells could be easily semi-quantified by immunostaining, with these results correlating with those obtained by qPCR. These results indicate that immunostaining for BCL-XL and MCL1 upon bone marrow examination at diagnosis not only can predict susceptibility to VEN + AZA therapy, but may also be useful for patient stratification for VEN + AZA treatment in the future.