Acute lymphoblastic leukemia (ALL) in infants (<1 year of age) remains one of the most aggressive types of childhood hematologic malignancy. The majority (~80%) of infant ALL cases are characterized by chromosomal translocations involving the (or ) gene, which confer highly dismal prognoses on current combination chemotherapeutic regimens. Hence, more adequate therapeutic strategies are urgently needed. To expedite clinical transition of potentially effective therapeutics, we here applied a drug repurposing approach by performing in vitro drug screens of (mostly) clinically approved drugs on a variety of human ALL cell line models. Out of 3685 compounds tested, the alkaloid drug Camptothecin (CPT) and its derivatives 10-Hydroxycamtothecin (10-HCPT) and 7-Ethyl-10-hydroxycamtothecin (SN-38: the active metabolite of the drug Irinotecan) appeared most effective at very low nanomolar concentrations in all ALL cell lines, including models of -rearranged ALL ( = 3). Although the observed in vitro anti-leukemic effects of Camptothecin and its derivatives certainly were not specific to -rearranged ALL, we decided to further focus on this highly aggressive type of leukemia. Given that Irinotecan (the pro-drug of SN-38) has been increasingly used for the treatment of various pediatric solid tumors, we specifically chose this agent for further pre-clinical evaluation in pediatric -rearranged ALL. Interestingly, shortly after engraftment, Irinotecan completely blocked leukemia expansion in mouse xenografts of a pediatric -rearranged ALL cell line, as well as in two patient-derived xenograft (PDX) models of -rearranged infant ALL. Also, from a more clinically relevant perspective, Irinotecan monotherapy was able to induce sustainable disease remissions in -rearranged ALL xenotransplanted mice burdened with advanced leukemia. Taken together, our data demonstrate that Irinotecan exerts highly potent anti-leukemia effects against pediatric -rearranged ALL, and likely against other, more favorable subtypes of childhood ALL as well.
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http://dx.doi.org/10.3390/biomedicines9070711 | DOI Listing |
Cancer Biol Ther
December 2025
Department of Hematology, Taixing People's Hospital Affiliated to Yangzhou University, Taixing, China.
Objectives: Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.
Methods: CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter.
Acute lymphoblastic leukemia (ALL) is a malignant condition of lymphoid progenitor cells that primarily affects the pediatric population, but also adults. The 5-year survival rate is 90% in children and approximately 40% in adults, with survival increasing through the use of peripheral stem cell allotransplantation (SCT). The relapse rate after stem cell transplantation (SCT) in adult acute lymphoblastic leukemia (ALL) patients ranges from 35% to 45%, making relapse a major cause of death in this population.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Experimental Oncology Laboratory, National Institute of Pediatrics, Mexico City 04530, Mexico.
Acute lymphoblastic leukemia (ALL) is a malignant neoplasm with the highest incidence in the pediatric population. Although the 5-year overall survival is greater than 85%, in emerging countries such as Mexico, the mortality rate is high. In Mexico, B-ALL is the most common type of childhood cancer; different characteristics suggest the presence of the disease; however, the prognosis is dependent on clinical and laboratory features, and no adverse prognostic molecular marker for B-ALL has yet been identified.
View Article and Find Full Text PDFChildren (Basel)
January 2025
2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece.
gene polymorphisms (677C>T and 1298A>C) correlate with various types of cancer across all age groups; however, a small number of studies have included solely children and adolescents. The aim of this systematic review and meta-analysis was to present and synthesize all the available evidence on the association between gene polymorphisms and the incidence of all types of cancer in children and adolescences. After a systematic search of all of the available data, original case-control studies involving children or adolescents with a confirmed diagnosis of any type of cancer and a molecular genetic test of gene polymorphisms were included.
View Article and Find Full Text PDFChildren (Basel)
December 2024
Department of Oncology and Hematology, Children's Hospital Zagreb, Klaićeva 16, 10000 Zagreb, Croatia.
: Recent advances in childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) management provide higher survival rates at the cost of increased toxicities. Acute neurotoxicity affects up to 10% of patients, requiring rapid recognition and treatment. : A retrospective observational study was performed to determine the frequency, clinical manifestations, radiological characteristics, treatment options and outcome of acute neurological adverse events in pediatric patients with lymphoid malignancies at the Department of Oncology and Hematology, Children's Hospital Zagreb, Croatia.
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