Patients with concurrent acute myeloid leukemia (AML) and active pulmonary tuberculosis (TB) exhibit certain characteristics; cough, phlegm, fever, hemoptysis, weight loss and dyspnea are common symptoms of both diseases. These patients often cannot tolerate traditional intensive chemotherapy regimens, and finding the optimal timing in the treatment of both AML and active pulmonary TB is complex. Neglecting timely treatment can lead to serious complications and even fatal outcomes. The present paper reports two cases of patients with AML who were diagnosed with active pulmonary TB. The patients received intensive anti-TB treatment with isoniazid, rifampicin, pyrazinamide and ethambutol for 10-15 days. After three consecutive negative sputum smears, the patients in cases 1 and 2 were treated with a venetoclax, homoharringtonine and cytarabine regimen; and a venetoclax and azacitidine regimen for anti-AML therapy, respectively, as well as individualized anti-TB regimens of isoniazid, pyrazinamide, ethambutol and quinolone. Subsequently, both patients achieved complete remission of AML and their active TB was well controlled.
Copyright: © 2024 Ji et al.

The blast crisis (BC) is the final deadly phase of chronic myeloid leukemia (CML), which remains a major challenge in clinical management. However, the underlying molecular mechanism driving blastic transformation remains unclear. Here, we show that ASF1A, an essential activator, enhanced the transformation to CML-BC by mediating cell differentiation arrest. ASF1A expression was aberrantly increased in bone marrow samples from CML-BC patients compared with newly diagnosed CML-chronic phase (CP) patients. ASF1A inhibited cell differentiation and promoted CML development in vivo. Mechanistically, we identified ASF1A as a coactivator of the Notch transcriptional complex that induces H3K56ac modification in the promoter regions of Notch target genes, and subsequently enhanced RBPJ binding to these promoter regions, thereby enhancing Notch signaling activation to mediate differentiation arrest in CML cells. Thus, our work suggests that targeting ASF1A might represent a promising therapeutic approach and a biomarker to detect disease progression in CML patients.
© 2022. The Author(s).