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 ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG's interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention.
© 2023. Springer Nature Limited.

Acute promyelocytic leukemia (APL) during pregnancy is rare and difficult to treat. To the best of our knowledge, there is little precedent for successful treatment with combined chemotherapeutic agents without affecting delivery. The present study reported the case of a 31-year-old woman pregnant with twins who presented to the antenatal service at 13-week gestational age with complaints of vaginal bleeding, lower abdominal pain, bleeding gums and skin ecchymosis, and was eventually diagnosed with APL. After treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction regimen, the patient achieved a complete remission (CR) and delivered two healthy male infants at 34 weeks of gestation. The use of ATRA and ATO for the treatment of APL is controversial due to teratogenic effects and lethal retinoic acid syndrome. However, the patient demonstrated that the chemotherapy regimen with ATRA and ATO during the second and third trimesters can result in a sustainable remission and successful pregnancy outcome.
Copyright © 2020, Spandidos Publications.

Acute megakaryoblastic leukemia (AMKL) is a rare disease, occurring mostly in infants and young children. The chromosomal translocation t(1;22)(p13;q13), resulting in the RBM15-MKL1 fusion gene, is a recurrent and diagnostic translocation in infants with AMKL. The present case report describes a case of a newborn girl, without Down's syndrome, with congenital AMKL. At birth, the infant had hepatosplenomegaly and the peripheral blood count revealed anemia, thrombopenia and leukocytosis, with 28% blasts. Immunophenotyping demonstrated blasts positive for CD34, CD61 and CD42b. Karyotyping of these blasts (R-banding) showed a hitherto unreported chromosomal translocation, t(1;7;22)(p13;q21;q13), a 3-way variant of the t(1;22)(p13;q13) variant. Fluorescent in situ hybridization analysis confirmed the presence of the RBM15-MKL1 fusion gene.
Copyright: © Messiaen et al.

Transcription factor Wilms' tumor gene 1 (WT1) is an ideal tumor target based on its expression in a wide range of tumors, low-level expression in normal tissues and promoting role in cancer progression. In clinical trials, WT1 is targeted using peptide-based or dendritic cell-based vaccines and T-cell receptor (TCR)-based therapies. Antitumor reactivities were reported, but T-cell reactivity is hampered by self-tolerance to WT1 and limited number of WT1 peptides, which were thus far selected based on HLA peptide binding algorithms.
In this study, we have overcome both limitations by searching in the allogeneic T-cell repertoire of healthy donors for high-avidity WT1-specific T cells, specific for WT1 peptides derived from the HLA class I associated ligandome of primary leukemia and ovarian carcinoma samples.
Using broad panels of malignant cells and healthy cell subsets, T-cell clones were selected that demonstrated potent and specific anti-WT1 T-cell reactivity against five of the eight newly identified WT1 peptides. Notably, T-cell clones for WT1 peptides previously used in clinical trials lacked reactivity against tumor cells, suggesting limited processing and presentation of these peptides. The TCR sequences of four T-cell clones were analyzed and TCR gene transfer into CD8+ T cells installed antitumor reactivity against WT1-expressing solid tumor cell lines, primary acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples.
Our approach resulted in a set of naturally expressed WT1 peptides and four TCRs that are promising candidates for TCR gene transfer strategies in patients with WT1-expressing tumors, including AML and ovarian carcinoma.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.