Background: The purpose of the current study was to evaluate the cytogenetic features of the hypodiploid leukemic cells of pediatric patients with this rare subgroup of acute lymphoblastic leukemia (ALL). In addition, the authors determined whether subdivision of the hypodiploid category served a prognostic purpose for these patients.
Methods: The authors evaluated the cytogenetic records of 979 patients with ALL admitted to St. Jude Children's Research Hospital (Memphis, TN) between 1984 and 1999.
Results: Of 67 patients (6.8%) whose leukemic cells contained a modal number (MN) of chromosomes less than or equal to 45 (i.e., hypodiploid leukemic cells), 57 had an MN of 45 and 10 had an MN of less than 45. In 19 patients, cells with an MN of 45 had a whole chromosome missing (42%), which was a sex chromosome in 12 patients (63%). Leukemic cells with an MN of 45 contained dicentric chromosomes (n = 33) formed from chromosome 9p (55%), 12p (18%), or both (21%). The ETV6-CBFA2 fusion was present in 39% of 28 evaluable B-lineage cases with an MN of 45. The event-free survival rate (EFS) for patients with hypodiploid leukemic cells of MN less than 45 (5-year EFS = 20.0% +/- 10.3%) was significantly (P < 0.001) lower than that for patients with leukemic cells of MN greater than or equal to 45 (5-year EFS = 74.9% +/- 1.6%).
Conclusions: Low hypodiploidy (MN < 45) should be recognized as a high-risk feature in pediatric ALL. Only two hypodiploid groups (MN < 45 and MN = 45) may be necessary in prognostic assessments.
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http://dx.doi.org/10.1002/cncr.11841 | DOI Listing |
Exp Hematol Oncol
December 2024
Department of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA, USA.
Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 - blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs).
View Article and Find Full Text PDFCancer Med
January 2025
Division of Oncology, The Children's Hospitial of Philadelphia, Philadelphia, Pennsylvania, USA.
Background: Single antigen (Ag)-targeted immunotherapies for acute lymphoblastic leukemia (ALL) are highly effective; however, up to 50% of patients relapse after these treatments. Most of these relapses lack target Ag expression, suggesting targeting multiple Ags would be advantageous.
Materials & Methods: The multi-Ag immune responses to ALL induced by transducing cell lines with xenoAgs green fluorescent protein and firefly luciferase was elucidated using flow cytometry, ELISA, and ELISpot assays.
Discov Med
December 2024
Department of Biological Hematology, Tours University Hospital, 37000 Tours, France.
Aldehyde dehydrogenases (ALDHs) constitute a group of enzymes that catalyze the oxidation of aldehydes to carboxylic acids. The human ALDH superfamily, including 19 different isoenzymes (ALDH1A1, ALDH1A2, ALDH1A3, AHDH1B1, ALDH1L1, ALDH1L2, ALDH2, ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, ALDH8A1, ALDH9A1, ALDHA16A1, ALDH18A1), displays different key physiological and toxicological functions, with specific tissue expression and substrate specificity. Several studies have established that ALDH are interesting markers for the identification and quantification of human hematopoietic stem cells and cancer stem cells, notably leukemic stem cells.
View Article and Find Full Text PDFCancer Sci
December 2024
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
In this study, we investigated the measurable residual leukemic stem cell (MR-LSC) population after allogeneic stem cell transplantation (allo-SCT) for high-risk acute myeloid leukemia (AML), utilizing T-cell immunoglobulin mucin-3 (TIM-3) expression as a functional marker of AML leukemic stem cells (LSCs). Analysis of the CD34CD38 fraction of bone marrow cells immediately after achievement of engraftment revealed the presence of both TIM-3LSCs and TIM-3 donor hematopoietic stem cells (HSCs) at varying ratios. Genetic analysis confirmed that TIM-3 cells harbored patient-specific mutations identical to those found in AML clones, whereas TIM-3 cells did not, indicating that TIM-3CD34CD38 cells represent residual AML LSCs.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Immunology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Toronto General Hospital Research Institute, Ajmera Transplant Centre, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address:
Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.
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